cord-000137-idffrnac	2009	The study further found that the induction of the negative regulators of TLR signaling IL-1R-associated kinase-M, Toll-interacting protein and A20 by intratracheal LPS in vivo and in macrophages in vitro was significantly reduced in CD44 -/mice. Thus, the study demonstrates a novel mechanism underlying HS-augmented lung inflammation, namely that induction of increased TLR2 surface expression in lung endothelial cells, which is induced by HS/R and mediated by HMGB1 activation of TLR4 signaling, is an important mechanism responsible for EC-mediated inflammation and organ injury following HS (122) . These results provide evidence for direct activation of the NLRP3 inflammasome by biglycan and suggest a fundamental paradigm of how tissue stress and injury are monitored by innate immune receptors detecting the release of the extracellular matrix components and turning such a signal into a robust inflammatory response (147) .
cord-000217-chd9ezba	2010	Furthermore, intratracheal treatment of CD14-defi cient mice with sCD14 restored the infl ammatory response to the level present in wildtype mice, whereas treatment with wild-type alveolar macrophages restored the neutrophil infi ltration of the lung but not pulmonary TNF release [26] . Th ese fi ndings indicate that sCD14, and CD14 and TLR4 on the surface of alveolar macrophages contribute to the development of LPS-induced lung infl ammation. In line with the fi ndings that CD14 contributes to LPSinduced lung infl ammation in mice, a number of studies have shown that CD14 is essential for the host defense response in the lung against Gram-negative bacteria, such as nontypeable Haemophilus infl uenzae, a possible cause of community acquired pneumonia, and A. coli-induced pneumonia has not been investigated in mice, whereas the role of the other components of the LPS receptor complex (TLR4, MD-2, MyD88, TRIF) has been determined using gene-defi cient or mutant mice.
cord-000425-isw6jeir	2011	A study on Yorkshire pigs selected for eight generations for high and low adaptive IR (HIR and LIR, respectively) on an index combining four standardized measures of specific antibodies and cellmediated IR, after stimulation with specific antigens (bacillus Calmette-Guérin and hen egg white lysozyme), has revealed that HIR and LIR animals differ in response to immunization and infection [2, 11, 12, 13, 14] . Finally, several significant QTLs for total leukocyte count ( [20, 21] ; Animal-QTLdb, http://www.animalgenome.org/cgi-bin/QTLdb/index), mitogen-induced proliferation [20] , antibody response [20, 22] , cytokine production (IL10 and IFNc) [23] , complement activity [22] , and acute phase protein serum concentration [22] have been detected and mapped to different pig chromosomes. In this report, we present the results of a global genetic study, combining principal component analysis (PCA), and genetic parameter estimation applied to a large number of innate and adaptive ITs in a pig population vaccinated against Mycoplasma hyopneumoniae (M.
cord-000460-h3owwjao	2011	However, with LPS stimulation numbers of platelets staining positive for both plateletand leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. Alternatively, comparable activation of leukocyte as well as platelet result in formation of cell-derived microvesicles (MV) which may contribute to increased thrombogenic propensity of the blood, pro-inflammatory immune processes and thus cardiovascular risk [15, 16, 17, 18, 19, 20, 21, 22] . Therefore, the present study was designed to test the hypothesis that acute exposure to a sentinel dose of LPS would induce MV production and exchange of specific proteins/ receptors between platelets and leukocytes via TLR4 activation. The acute effects of LPS on platelet and leukocyte activation were most likely mediated through activation of TLR4 as platelet positive leukocyte antigen was not observed in blood from dTLR4 mice. Platelet-leukocyte interactions require TLR4 signaling as the dual antigen positivity of platelets was observed in blood derived from wild type but not dTLR4 mice.
cord-000920-68eblcke	2013	The nasal septa of fetal rabbits at 26 days of gestation were harvested by cesarean section of the does while under anesthesia and then exposed to Bordetella bronchiseptica or its lipopolysaccharide (LPS) for periods of 2 and 4 hours. Bordetella bronchiseptica is a Gram-negative bacterium capable of colonizing the respiratory tract of a large range of mammalian hosts, including mice, rats, guinea pigs, rabbits, cats, dogs, pigs, sheep, horses, and bears [1] . bronchiseptica or its LPS in an isolated manner by using a model that more closely reflects the in vivo conditions (i.e., reconstructing the architecture and cell relationships of the respiratory epithelium in a natural host of this microorganism) has not been documented. In this work, LPS induced a higher infiltration of PMN in the respiratory epithelium and the propria of nasal septa than did the bacterium. B. bronchiseptica and its LPS distribution on the nasal septum respiratory epithelium were evaluated by the indirect immunoperoxidase and lectin histochemistry techniques.
cord-000959-nk2thkme	2013	METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). The purpose of the study was to compare the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and the response of these cells to LPS in samples prepared from the LP cohort and a cohort which we classified as IQ memory-consistent (high-performing, HP) individuals. P) TLR4 expression on CD11b + MDMs was increased in the LP group compared with the HP group (P,0.05) and this is also shown in the representative dot plots of TLR4 + cells ( and following LPS stimulation [6] , while pro-inflammatory cytokine [52] and chemokine [53, 54] levels are elevated in peripheral blood monocytes isolated from the elderly after LPS stimulation.
cord-000984-64p3wpav	2013	We herein further demonstrate that rCRT fragments 18–412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50–100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro. Additionally, rCRT/39-272, a prokaryotically-expressed murine CRT fragment covering amino acid residues 39-272 fused with an N-terminal His-tag, was extraordinarily potent in activating B cells and macrophages in vitro and also in eliciting specific Ab production in mice [16] . The sequence of rCRT/39-272 encompasses most of the globular N domain (aa residues , and we have previously shown that it possess lectin-like activity (selective binding with polysaccharides including carrageenan, alginic acids, and hyaluronic acids in ELISAs) [16] , implying that the prokaryotically expressed recombinant polypeptide retained the lectin activity of CRT. Purified nCRT, but not BSA or recombinant enhanced green fluorescence protein (rEGFP, 28 kDa with a His-tag), was positively recognized by CRT-Abs. As evidenced by native PAGE analysis, a substantial amount of rCRT/18-412 formed higher-molecular-weight oligomers, whilst nCRT existed mostly in monomeric form (Figs.
cord-001496-186k6t03	2014	Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, the number of myeloperoxidase (MPO) positive cells, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1), gene expression of ICAM-1, ultrastructure changes of pulmonary microvasculature, concentration of inflammatory markers and in plasma. RESULTS: Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils and hemorrhage, the increase in lung W/D ratio, the number of MPO positive cells, the level of inflammatory markers such as TNF-α, MCP-1 and IL-8, enhanced expression of ICAM-1 and ICAM-1 gene. CONCLUSIONS: These results indicate that Ginsenoside Rb1 attenuated LPS-induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on proinflammatory molecules. The goal of the present study was to clarify the effects of Ginsenoside Rb1 on LPS-induced rat lung injury and analyzed the detailed molecular mechanisms in vivo and in vitro.
cord-001569-jd028cyg	2015	We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim(−/−) mice challenged with LPS, bleomycin and asbestos. Exposure to bleomycin resulted in a large increase in immune cells in the airspace of both WT and Vim À / À mice as assessed by flow cytometric analysis of whole-lung lysates ( Supplementary Fig. 3a ). All together, these results suggest that vimentin-expressing bone marrow-derived cells are important for bleomycin-induced activation of the NLRP3 inflammasome and pulmonary fibrosis. Studies with IL-1R1 À / À , MyD88 À / À , ASC À / À , Caspase-1 À / À and NLRP3 À / À mice have suggested that uric acid (induced by bleomycin), asbestos and silica are detected by the NLRP3 inflammasome in macrophages, likely leading to IL-1R1/MyD88 signalling in pulmonary epithelial cells, then to inflammation, neutrophil and lymphocyte recruitment and fibroblast activation 35 .
cord-002079-jne14jqf	2016	Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. These data demonstrate that certain inflammatory stimuli (TNF-␣ and LPS), as well as ischemic injury, but not other cytokines (IL-6 and IL-10) can lead to enhanced hepatocyte USP18 expression and thereby inhibit IFN signaling. Huh7.5 cells and primary murine hepatocytes were treated with IFN-␣ (100 U/ml), TNF-␣ (20 ng/ml), LPS (100 ng/ml), IL-6 (100 ng/ml), or IL-10 (10 ng/ ml) over a 24-h time course, and USP18 expression was determined by quantitative PCR (qPCR) as previously described (8, 9) .
cord-002165-blbaqbo7	2016	title: Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. A previous study conducted by our group observed caspase-1 activation in AMs during the development of ALI/ ARDS, and further, that treatment with a specific caspase-1 inhibitor has been shown to reduce LPS-induced lung injury in mice (8) . In the present study, we showed that the absence of IRF-1 in genetic knockout mice strongly alleviates LPS-induced lung injury and abrogates its pyroptotic effects in AMs. These findings suggest that IRF-1 plays a key role in controlling caspase-1-dependent pyroptosis and inflammation, which is, in turn, a TLR4-dependent process.
cord-002411-iiw878w8	2017	The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli. To address the effect of LPS/TLR4-mediated activation of TLR3 in AMΦ on inflammatory cytokines, we assessed TNF-α and IL-6 in the serum and BALF, as well as the chemokines MIP-2 and MCP-1 in the BALF, following sequential intratracheal challenges with LPS and Poly I:C. This cross talk between TLR4 and TLR3 in AMΦ resulted in the amplification of cytokine (IL-6, TNF-α ) and chemokine (MIP-2, MCP-1) expression in response to LPS and Poly I:C, which activate TLR4 and TLR3, respectively, and subsequently led to enhanced PMN sequestration into the lung, which was found to be correlated with ALI based on the assessment of alveolar-capillary permeability and histological sections of lung tissue.
cord-003055-88q36g00	2018	The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Since MIA has been considered to be a cause of behavioral abnormalities in offspring, including ASD/ Schizophrenia-like behavior, we subsequently evaluated the effect of LPS and maternal administration of HW on short-term memory, sociability, social novelty, and sensorimotor gating. Based on those findings, we subsequently performed Nissl staining and evaluated the number of neurons in the amygdala, cerebral cortex, and hippocampus to investigate the brain regions related to the results of the behavioral deficits induced by LPS exposure.
cord-003099-a0acr28o	2018	In vitro studies in which influenza-infected alveolar macrophages were subsequently stimulated with bacterial lipopolysaccharide (LPS), a bacterial compound that induces a profound innate immune response, revealed increased levels of pro-inflammatory cytokines tumor necrosis factor (TNF) α, interleukin (IL)-1β, and IL-6 [4] [5] [6] [7] [8] , indicative of a priming effect on these cells by influenza. Likewise, murine influenza infection resulted in increased levels of pro-inflammatory cytokines in both plasma and lungs, and enhanced pulmonary neutrophil influx upon pneumococcal infection 7 days later [10] . In the present study, we demonstrate that a systemic LPS challenge in the acute phase of influenza infection (4 days post-infection) results in an enhanced pulmonary, but not systemic pro-inflammatory cytokine response. Our results are in accordance with in vitro data reporting a cellular priming effect of influenza observed upon secondary stimulation with LPS [4] [5] [6] [7] [8] , as well as with other murine in vivo studies that report increased inflammation and pulmonary neutrophil influx or sequestration upon a secondary bacterial infection or LPS challenge in the acute phase of influenza infection [9, 10] .
cord-004067-psjyjvbu	2019	Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified. The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation. In the current study, the p110α isoform in PI3K/AKT/mTOR signalling pathway was demonstrated to be involved in miR-21a-3p-mediated angiogenic factor induction in TCs. However, the alteration of other protein levels and HIF-1α in TCs treated with LPS and the miR-21a-3p inhibitor indicated that more complex signalling pathways were involved in regulating the angiogenic function of TCs. Culture medium from LPS-induced TCs promoted EOMA cells proliferation in vitro, accompanied by elevated levels of VEGF mRNA and secretion, which further demonstrated that the functional miR-21a-3p was generated by TCs. These data support the hypothesis that miR-21a-3p plays a role in angiogenesis and profoundly demonstrate the mechanisms mediated by PI3K p110α.
cord-004140-ujzrqzv3	2020	As a selective phosphodiesterase-4 inhibitor, rolipram also exhibits the abilities of inhibiting multiple pro-inflammatory cytokines production in macrophages and toxin-induced inflammation in mice. Therefore, the serum levels of multiple pro-inflammatory cytokines Male C57BL/6 mice were injected with different doses of rolipram (1 mg/kg, 5 mg/kg, and 10 mg/kg, i.p.) 1 hr before LPS injection. We demonstrate that rolipram may protect against LPS-induced inflammation and shock in mice, likely through the inhibition of the NF-κB and MAPK signaling pathways. We have found that rolipram inhibits pro-inflammatory cytokines and chemokines released by the administration of LPS, leading to the suppression of excessive inflammatory responses, cell adhesion and migration, and the further sequelae of shock and multiple organ failure in the mouse host. Our results indicated that rolipram suppresses LPS-induced ERK, JNK, and p38 MAPK phosphorylation in lung tissue, suggesting that the MAPK signaling pathway -as well as NF-κB -may mediate the anti-inflammatory actions of rolipram.
cord-004282-tox3tuzz	2019	Therefore, the aims of our study were to evaluate the basal level of expression of pivotal genes in the innate immune response and cell cycle regulation, as well as to evaluate the ability of this cell line to respond to infectious or non-infectious stressors. However, little is known about basal expression of genes involved in innate immunity, DNA repair, cell cycle regulation, as well as in the secretion of cytokines, and the response to infectious and non-infectious stressors. Owing to the above, the aims of our study were: 1-to evaluate the basal level of expression of pivotal genes in the innate immune response and cell cycle regulation. Moreover, in our previous study we demonstrated the ability of this heavy metal to modulate innate immune responses in IPEC-J2 cells as a function of both time and concentration (Razzuoli et al.
cord-004754-5596p4ma	2014	title: Effects of origin and state of differentiation and activation of monocytes/macrophages on their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) To evaluate the effect of maturation of monocytes/macrophages on their susceptibility to PRRSV, freshly isolated AMf, PMf and BMo from ®ve donors were seeded in 24-well tissue culture plates at a concentration of 10 6 cells/ml/well and further incubated in RPMI medium plus 5% of foetal bovine serum at 37 C with 5% CO 2 . The virus titres and percentage of viral antigen positive cells in freshly isolated porcine AMf at 24 and 48 h after inoculation were respectively 1 to 2 log 10 TCID 50 and 5 to 10 times lower than those of one day cultivated ones, which is signi®cantly different (P''0.01). Porcine reproductive and respiratory syndrome virus infection of alveolar macrophages can be blocked by monoclonal antibodies against cell surface surface antigens
cord-005497-w81ysjf9	2020	The positive NC group had more plasma transfusion (p-value 0.03) and a lower median hematocrit at 24 hrs (p-value 0.013), but similar hospital length of stay (p=0.17) and mortality rate (p=0.80) Conclusions: NC at ICU admission identifies subclinical AKI in TBI patients and it maight be used to predictclinical AKI. In patients with pneumonia requiring intensive care (ICU) admission, we hypothesise that abnormal right ventricular (RV) function is associated with an increased 90-day mortality. The objective of this study was to describe the incidence of each AKI stages as defined by KDIGO definition (with evaluation of urine output, serum creatinine and initiation of renal replacement therapy (RRT)), in a mixed medical and surgical population of patients hospitalized in ICU and PCU over a 10-year period (2008-2018). This study aimed at investigating the relationship of goal-directed energy and protein adequacy on clinical outcomes which includes mortality, intensive care unit(ICU) and hospital length of stay (LOS), and length of mechanical ventilation (LOMV).
cord-005607-b1a39hhw	2000	Over the last three decades we have gained significant insights into leukocyte activation, recruitment and mediator secretion and the contribution of these agents to both the onset and resolution of sepsis and inflammation.¶The body relies on the inflammatory response for protection. A direct consequence of this protective strategy is that the inflammatory response may be inadequate, with the risk of overwhelming sepsis, or excessive, leading to rampant systemic inflammation and consequent multiple organ damage.¶It is now becoming apparent however that in addition to leukocytes other cells have important roles both in defence against invading pathogens and in driving malignant inflammation. Endothelial cells, mesothelial cells, fibroblasts and epithelial cells are also all involved not only with their capacity to drive the inflammatory response through mediator generation but also in innate immune defences including through the production of antimicrobial proteins.
cord-005727-li8pwigg	2010	Since, continuous epidural analgesia provides the required level of analgesia to support early mobilization and significant reduction in pulmonary and cardiovascular morbidity in the early postoperative period, we postulated that the use of low dose of continuous epidural morphine might improve postoperative analgesia and reduce undesirable side effects in elderly patientsTherefore, the present study was designed to evaluate the effects of morphine administered via epidural patients controlled analgesia and intravenous tramadol + metamizol on postoperative pain control and side effects in elderly patients after major abdominal surgery. For each ventilated patient the following data was registered:Age, APACHE II, the reason of admission, risk factors, use NIV, MV duration, timing of tracheostomy, time of diagnosis of VAP, microbiological data, length of stay and mortality in ICU. 23rd ESICM ANNUAL CONGRESS -BARCELONA, SPAIN -9-13 OCTOBER 2010 S131 Evaluated factors: patient characteristics, signs, symptoms, abscess location, time between symptoms and hospital admission and surgery, lab results, microbiology, antibiotic therapy, APACHE2, SAPS2, SOFA, length of ICU stay, surgical re-intervention, duration of mechanical ventilation, infectious complications, critical illness myopathy (CIM), renal replacement therapy (RRT), re-intubation, tracheotomy, mortality.
cord-005814-ak5pq312	1995	Results: In 5 patients with treated SS, 16 tests were performed (VL n=8; Dobu n=4; NA n=4 Method: Septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; MAP<70 mmHg) or the requirement for a noradrenaline (NA) infusion ~> 0.1 ~g/kg/min with a MAP _< 90mmHg. Cardiovascular support was limited to NA + dobutamine (DB), 546C88 was administered for up to 8 h at a fixed dose-rate of either i, 2.5, 5, 10 or 20 mg/kg/h iv. Methods: Fourteen cases were s~udied,their gestational age ranged from(27-32)ws.Continnous positive air way pressure was applied to six cases at Peep level from (3-6)cm H2o through nasal pronge,(group I),the other 8 cases were managed as routine,(group II).Blood gases, TcPO2,TcCo2,resp.rate,depth and pattern were monitored for assessment of tissue Oxygenation and ventilation, Results: Our rasults showed that early application of CPAP improve ventilation among (83.3%)of cases,while (16.7%)of cases need IMV.The cases of group II need IMV among (75%)of the studied cases during the second or the third day of life.
cord-005832-p1joajvn	2013	The purpose of this study was to evaluate the effect of gossypol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Additionally, gossypol reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs and inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS. CONCLUSION: The data suggest that anti-inflammatory effects of gossypol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPKs signaling pathways. The results showed that pretreatment with gossypol attenuated lung damage induced by LPS and decreased the W/D ratio, proinflammatory cytokine production, inflammatory cell migration into the lung, protein leakage, the activation of NF-jB and MAPK. In conclusion, the present study demonstrated that gossypol has a protective effect against LPS-induced ALI, which may be related to its suppression of NF-jB and MAPKs activation, and subsequently leads to the reduction the inflammatory cell infiltration and proinflammatory cytokine expression in lung tissues.
cord-005872-w1x1i0im	2000	Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies. S. aureus has been reported to directly infect human umbilical vein endothelial cells (HUVEC) thereby inducing secretion of cytokines and functional upregulation of adhesion molecules [2] . Infection and activation of endothelial cells by Listeria monocytogenes is believed to be a critical component of the pathogenesis of this disease and includes ceramide generation, transcription factor activation and increases in adhesion molecule expression on HUVEC [11] . E-selectin expression in human endothelial cells by TNF-alpha-induced oxidant generation and NF-kappaB activation
cord-005875-yp1ehpeg	2020	OBJECTIVE: To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs). RESULTS: This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factor κB, and mitogen-activated protein kinase in vivo and in vitro. The preceding results indicated that crocin might inhibit the expression of HPA by inhibiting the upstream protein of CTL in LPS-induced ARDS mice and LPS-stimulated HUVECs. The results in vivo showed that the expression of MMP-9 by LPS stimulation was significantly increased compared with that of the control group (Fig. 4c, d) . These results suggested that crocin can inhibit the activation of MAPK pathway in LPS-induced ARDS mice and LPS-stimulated HUVECs. The HMGB1 and NF-κB signaling pathway also regulate lung injury of the inflammatory process.
cord-005980-e2s0racp	2019	Twenty-four hours later, lung bronchoalveolar lavage fluid (BALF) was acquired to analyse cells and protein, arterial blood was collected for arterial blood gas analysis and the determination of pro-inflammatory factor levels, and lung issues were collected for histologic examination, transmission electron microscopy (TEM), TUNEL staining, wet/dry (W/D) weight ratio analysis, myeloperoxidase (MPO) activity analysis and blot analysis of protein expression. RESULTS: We found that TIPE2 overexpression markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression in the BALF. CONCLUSIONS: Our study shows that the increased expression of AAV-mediated TIPE2 in the lungs of mice inhibits acute inflammation and apoptosis and suppresses the activation of NF-κB and JNK in a murine model of ALI. Compared with those in the control group, the PMN/total cell ratio in the BALF (Fig. 4c) and lung MPO activity (Fig. 4d) in LPS-challenged mice were dramatically increased, and these levels were inhibited by AAV-TIPE2 treatment.
cord-006229-7yoilsho	2016	It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1).
cord-006230-xta38e7j	2012	Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure.
cord-006279-ib5z3elq	2002	Recent studies have discovered a potent anti-inflammatory effect of CO: the inhibition of pro-inflammatory cytokine production following inducing stimuli, dependent on the modulation of mitogen activated protein kinase (MAPK)signaling cascades [6, 11] . This review will (I) describe the regulation of HO-1 as an inducible source of endogenous CO, (II) describe evidence that HO-1 acts as a mediator of cellular and tissue protection against oxidative stress, and (III) emphasize recent studies that introduce novel anti-apoptotic and anti-inflammatory properties of HO-derived CO in oxidative lung injury models. MKK3 mitogen activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury Activation of heme oxygenase and heat shock protein 70 genes by stress in human hepatoma cells Mitogen activated protein kinase (MAPK) pathway regulates heme oxygenase-1 gene expression by hypoxia in vascular cells
cord-006285-kkxdmzk9	2019	The present work reports the comparative assessment of the functional changes which take place in human ECV-304 endothelial cell sublines obtained previously by the long-term culturing of cells after exposure to varying infectious doses (IDs) of influenza A virus, and/or bacterial lipopolysaccharide (LPS). It has been demonstrated that, in the course of long-term culturing (six passages) after exposure to pathogenic agents (influenza virus and/or LPS), endothelial cells maintain changes in their migratory activity, permeability, and expression of mRNA for cytokines TNFα and TGFβ (along with the changes in their proliferation activity, which has been demonstrated earlier). The comparative study of the human endothelial ECV-304 cell sublines carried out in the present work and in our previous work (Smirnova et al., 2018) has demonstrated that the infection of nonpermissive cells with influenza A virus (both in high and in very low doses) and exposure to LPS can change migratory, proliferation, and apoptotic activity of cells and impair cell barrier function.
cord-006318-9r51n241	2013	During the 26 years that have elapsed since its discovery, activin-A, a member of the transforming growth factor β super-family originally discovered from its capacity to stimulate follicle-stimulating hormone production by cultured pituitary gonadotropes, has been established as a key regulator of various fundamental biological processes, such as development, homeostasis, inflammation, and tissue remodeling. [92] that prophylactic and therapeutic treatment with follistatin could improve the survival rate of mice in three mouse colitis models, attenuate several pathology-associated parameters and upregulate proliferation of intestinal epithelial cells and tissue repair, improving thus the barrier function of the colonic mucosa, strongly supported the association between activin-A and colitis pathophysiology [92] . The combination of aggravated innate immunity, activation of the coagulation system, and alterations in molecular systems crucial for homeostasis, such as the surfactants in the lung, can collectively lead to acute necroptotic cell death which leads to the release of highly pro-inflammatory complexes of DAMPs and cytokines that can activate via a feed-forward like response further activation of the TLR signaling pathway and further production of activin-A.
cord-006570-v4as5gde	2007	title: Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat LPS-INS animals showed a significantly greater bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, villus height in ileum, crypt depth in jejunum and ileum, cell proliferation rates in jejunum, and significantly lower apoptotic index in ileum compared to LPSanimals. The purpose of this study was to evaluate the effects of oral insulin in preventing mucosal damage caused by LPS endotoxemia in a rat model, including its effect on enterocyte proliferation and death via apoptosis, and to determine whether alterations in Toll-like receptor 4-mediated signaling may occur during LPS endotoxemia and insulin administration. Oral insulin increases the stimulating effect of LPS on Toll-like receptor 4 expression in the proximal intestine, suggesting that TLR4 is not the mediator of injury in this model.
cord-006605-tsk3pakb	2006	The hypothesis that the expression of protease-activated receptors (PARs) protein is regulated at the level of transcription and that PAR isoforms, PAR-1, PAR-2, PAR-3, and PAR-4, in lung tissue show different patterns of expression in lipopolysaccharide (LPS)-induced acute lung injury (ALI) was tested. LPS administration induced significant increases in the expression of PAR isoforms (protein) at the level of transcription in ALI. We conclude that LPS induces increase in protein expression of PAR isoforms at the level of transcription in rats with ALI. Here, we also found that LPS induces increases in the protein expression of PARs isoforms 1 to 4 in the lung of rats. While our previous study demonstrated the immunolocalization of PAR-1 in these cells and tissues in LPS-treated rabbits, the present study showed strong immunoreactivities for all isoforms of PARs in the endothelium, alveolar epithelium, and lung macrophages using a rat model of ALI [10] .
cord-006700-df8ard9o	2014	However, upon infectious or sterile inflammatory stimulation via either the alveolar (e.g., in pneumonia and mechanical ventilation) or the vascular lumen (e.g., in bacteremia and sepsis), pulmonary endothelial barrier homeostasis may be disturbed, resulting in increased permeability, protein-rich fluid extravasation, lung oedema and finally acute respiratory distress syndrome (ARDS) with mortality rates ranging from 27 to 45 % depending on severity (Ranieri, et al. Although the underlying mechanisms of leukocyte mediated barrier failure are of highest scientific interest, therapeutic interference to ameliorate acute lung injury by depletion or blocking of cell recruitment should raise concerns as neutrophils and monocytes are key players of pulmonary and systemic innate immune responses and therapeutic intervention at this level might leave the patient functionally immunosuppressed. In mice, Ang-1-induced Tie-2 receptor phosphorylation stimulated the p190RhoGTPaseactivating protein (p190RhoGAP) via PI3-kinase and Rac1 to inactivate RhoA, resulting in reduced F-actin stress fibre formation and diminished endothelial permeability (Mammoto et al.
cord-006778-qnxyhmw5	2017	Results showed that downregulation of PALM3 improved the survival rate, attenuated lung pathological changes, alleviated pulmonary edema, lung vascular leakage and neutrophil infiltration, inhibited the production of proinflammatory cytokines and activation of nuclear factor κB and interferon β regulatory factor 3, and promoted the secretion of anti-inflammatory cytokine interleukin-10 and expression of suppressor of cytokine signaling-3 in the ALI rat model. Adult Wistar rats (n = 6 per group) were treated as described in the BMaterials and Methods^section BEstablishment of ALI Rat Model and Experimental Design.^At 24 h after LPS challenge, the right lungs were harvested and stored in liquid nitrogen for the analysis of NF-κB phospho-p65, phospho-IRF3, TLR4, MyD88, TRIF, suppressor of cytokine signaling 3 (SOCS3) protein levels and coimmunoprecipitation assay, and the left lungs were harvested for the analysis of lung wet/dry weight ratio.
cord-006888-qfnukav4	2008	
cord-007178-h0ordzm9	2005	At this interval the lesion was clearly discernible using differential interference contrast optics as a region of tissue disruption in the dorsal funiculus, allowing AdPC-positive cells to be counted in both demyelinated and apparently normal areas of the dorsal funiculus of LPS-injected animals. Spinal cords injected with saline ( Fig. 1) showed damage restricted to a very small number of axons undergoing either Table 1 Populations of inflammatory cells present in the spinal cord at various times following the injection of LPS or saline into the dorsal funiculus Wallerian degeneration or demyelination. The cells were often adjacent to large blood vessels, and they formed only a small subset of the substantial population of ED1-positive Fig. 7 Light micrographs showing GFAP immunoreactivity at the interface between the dorsal funiculus (DF) and the grey matter (GM) in an animal 7 days after the injection of LPS into the spinal cord.
cord-009753-6rg47f0i	2015	Current medical treatments for conditions involving an impaired respiratory system provide inefficient methods of delivering oxygen to the patient. Previously, we have shown that peritoneal membrane oxygenation (PMO) with OMBs is a possible treatment method in acute lung injury models [2] . Our study involves two phases: (1) development and characterization of the ARDS disease model in rats; (2) design and validation of ambulatory infusion device. Phase 2 is the development of an ambulatory delivery system that will infuse fluid to the rat''s peritoneal cavity for treatment. We expect to be able to continuously dose saline, inert gas microbubbles (IMBs), and OMBs into the peritoneal cavity of four animals with the current PDS design. Based upon our previous animal experiments with lung injuries, we anticipate improved pulse oximetry, blood gases, and survivability in rats provided OMBs compared to those administered saline or IMBs. Intratracheal Aerosolization of Endotoxin (LPS) in the Rat: A Comprehensive Animal Model to Study Adult (Acute) Respiratory Distress Syndrome
cord-011286-8wxih7v6	2019	
cord-012487-s920s5wb	2020	By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. In order to understand how the model Gram-negative species Escherichia coli coordinates membrane synthesis with growth, we quantified substrates and enzymes of the fatty acid and PL synthesis pathways under both steady-state and dynamic conditions. The trends in substrate, enzyme, and intermediate concentrations observed in ppGpp-limited cultures are consistent with growth regulating PL flux via posttranslational control-not transcriptional control-of PlsB. To test whether regulation of PlsB activity is sufficient to control steady-state PL synthesis, we constructed a simplified differential equation model that describes fatty acid, LPS initiation, and PL biosynthesis ( Fig. 2A ; see also Text S1 and Table S1 ).
cord-012791-dyk5mr1q	2019	title: Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway Moreover, ICS II not only exerted the inhibitory effect on LPS-induced IκB-α degradation and NF-κB activation, but also decreased the levels of Aβ(1–40), Aβ(1–42), amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes. The present study revealed that (1) ICS II protects against LPSinduced inflammation in primary-cultured astrocytes; (2) the inhibitory effect of ICS II is due to regulation of the IKK/IκB/NF-κB signaling pathway; and (3) ICS II decreases Aβ 1-40 and Aβ 1-42 levels by downregulating APP and BACE1 expression (Fig. 7) . In conclusion, the current study revealed that ICS II exerts inhibitory effects on LPS-induced inflammation in astrocytes through the IKK/IκB/NF-κB/BACE1 signaling pathway, and thus ICS II may be a promising therapeutic agent for neuroinflammatory diseases, including AD.
cord-012828-wsjob1p8	2019	We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Some previous research has suggested that spinal cord injury induces inflammatory cytokine production by activating the nucleotide-binding domain-like receptor protein 3 inflammasome pathway, which is significantly suppressed by DRD1 agonists [14] . Therefore, in this study, we explored the mechanism of the anti-neuroinflammatory effects of isosibiricin in a BV-2 microglial model and highlighted that isosibiricin can significantly inhibit the production of multiple inflammatory mediators induced by bacterial lipopolysaccharide stimulation via targeting the DRD1/D2-dependent inflammasome pathway, providing a potential therapeutic strategy for inflammation-related neurological disorders. Isosibiricin inhibits the NLRP3/caspase-1 inflammasome pathway in LPS-or nigericin-treated BV-2 cells and LPS-treated Balb/c mice It has been reported that the expression of the pro-inflammatory mediator IL-1β significantly increases in DRD2-null mice compared with wild-type mice [24] .
cord-013067-sic08gsg	2020	Inhibition of Kv3.4 with the specific blocker BDS-I increased HPV in isolated perfused endotoxemic mouse lungs. Extracts of total lung tissue from mice with LPS i.p. showed an increase of Kv3.4 gene expression (3.9 ± 0.5fold, n = 6, mean ± SEM, p < 0.05) ( Fig. 1 ) in comparison to 0.9% NaCl solution treated controls (1.0 ± 0.2-fold, normalized on 1, n = 6, means ± SEM). In order to test the role of Kv3.4 in the pulmonary vasculature, lungs of mice with and without endotoxemia were perfused with and without 50 nM of the Kv3.4 specific inhibitor BDS-I. Since Nav1.7 expression is not described in pulmonary arteries, it reduces the possibility that the effect by 50 nM BDS-I in the isolated perfused mouse lung are provoked via inhibition of Nav1.7. An isolated, perfused mouse lung model was used to study pulmonary vasoreactivity in response to acute hypoxia in LPS exposed mice.
cord-013366-sbdtpsz6	2020	Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both proand anti-inflammatory cytokines. The chemical molecule ST2825 acts as an inhibitor of MyD88 dimerisation and its activity has been demonstrated through the inhibition of TLR9-dependent CpG-regulated signalling, and inhibition of IL-12, IL-1β, IL-6 and tumor necrosis factor alpha (TNF-α) expression in LPS-stimulated RAW 264.7 cells [19] [20] [21] [22] . The present study shows that the specific inhibition of critical components in the IL-1 signalling pathway is not enough to avoid the secretion of inflammatory mediators, the above suggests that various MyD88-independent mechanisms could regulate the production of cytokines in PBMC.
cord-013840-mi3uf4vk	2019	Specifically, Lamtor5 associated with TLR4 via their LZ/TIR domains and facilitated their colocalization at autolysosomes, preventing lysosomal tethering and the activation of mTORC1 upon LPS stimulation and thereby derepressing TFEB to promote autophagic degradation of TLR4. 16, 17 Loss of the autophagic components autophagy-related 16 like 1, Beclin1, and microtubule-associated protein 1A/1B light chain 3 (LC3) enhanced the macrophage response to LPS, a prototypical agonist of TLR4, and caused sustained inflammatory signaling. [26] [27] [28] A recent study identified Lamtor5 as an indispensable component of the Ragulator complex that interacts with small GTPase Ras-related GTP binding protein (RAG), contributing to lysosomal recruitment and the activation of mechanistic target of rapamycin complex 1 (mTORC1) in response to amino acids. j Immunoblotting for TLR4 and total and phosphorylated p65 in control and Lamtor5-expressing RAW264.7 cells pretreated with DMSO or Baf1 and then stimulated with LPS for the indicated time periods.
cord-014996-p6q0f37c	2009	Data recorded on admission were the patient demographics with, acute physiology and chronic health evaluation II score (APACHE II), and type of admission; during intensive care stay, sepsis-related organ failure assessment score (SOFA) and clinical concomitant factors and conditions. For each severe septic patient the following data was registered: time delay, APACHE II and SOFA scores at ICU admission, diagnosis, the rate of compliance with the resucitation and management bundles, microbiological data, evolution of levels of serum lactate, empiric antibiotic therapy, length of stay and mortality in ICU. Sepsis and septic shock remain the most important causes of acute kidney injury (AKI) in critically ill patients and account for more than 50% of cases of acute renal failure (ARF) in intensive care units (ICU). There were no significant differences between the demographic data (sex, age) or the data on admission to intensive care (APACHE II score, ratio of medical to surgical patients) and duration of mechanical ventilation between the two groups.
cord-015021-pol2qm74	1994	It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events.
cord-015082-l629n8is	2002	14 patients awaiting urgent cardiac surgical re-vascularisation were studied with measurement of: spirometry; percentage increase in transfer factor from sitting to lying position (TF) as an indicator of micro-vascular lung disease; overnight oximetry on air; and 24hour holter monitoring Patients, who were reintubated on decreased indices of arterial oxygenation under MOSF progressing died in 100% cases ( NIMV is effective method in complex therapy of ARF, developing in postoperative period after cardiac surgery, that leads to significant improvement of lungs biomechanics and gases change function. In a prospective observational study we performed bedside ptO2 measurements in 8 patients with sepsis/septic shock to gain insight in ptO2 values and their dynamic changes related to the course of the illness, as well as investigating the practical applicability of tissue oxygen measurement in the ICU setting.
cord-015147-h0o0yqv8	2014	Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis.
cord-015394-uj7fe5y6	2008	Studies involving immunohistochemical analysis of normal ovaries have shown that granulosa cells express significantly higher levels of the activator protein-1 (AP-1) transcription factor, cFos compared to theca cells, where cFos expression is virtually absent. Following acute hypoxia (0.5% O2) for one to six hours, RhoA mRNA, total protein and activation (RhoA-GTP) levels were analysed, using semi-quantitative PCRs and western blot, and compared to normoxic non-pregnant human uterine smooth muscle control cells. Since there is an urgent need for non-invasive methods for determination of fetal (F) and placental (P) function, this study was designed to evaluate the genes differently and commonly expressed in P tissue and leukocytes in maternal (M) and F circulation.Material and Methods. The current study: 1) localized IL-6 mRNA levels in preeclamptic versus normal decidual sections; 2) evaluated mechanisms regulating IL-6 synthesis by targeting intracellular signaling pathways with specific inhibitors; 3) identified potential IL-6 targets by immunolocalizing the IL-6 receptor (IL-6R) to specific cell types in placental bed biopsies.
cord-018969-0zrnfaad	2015	
cord-022136-3q24qxsr	2016	Treatment of B16 melanoma cells with lipopolysaccharide (LPS) or lipid A at 1 μg/ ml each for 48 h, which induced CCL2 expression, followed by extensive washing and subcutaneous implantation, reduced the tumor growth compared with untreated B16 cells in both wild-type and TLR4-KO mice. Expression of endogenous ligands, such as S100A8 and SAA3, in endothelial cells in sterile premetastatic lungs is induced by primary tumor-derived growth factors, such as CCL2, from the circulation side and the paracrine signaling goes in an opposite direction from the circulation to airway side to result in amplification of SAA3 in club cells. Detailed analysis of stimulation and expression pattern of S100A8, SAA3, and TNFα revealed that the triggering mechanism is primary tumor-secreted CCL2 that activates CCR2 in the hyperpermeable regions in the lungs to induce S100A8 expression in the endothelial cells.
cord-022252-9yiuuye3	2013	
cord-022888-dnsdg04n	2009	Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery.
cord-023026-2r84ndzv	2013	Thus, this work provides the basis to identify molecular pathways regulated by distinct niche/environmental signals and involved in the heterogeneity of adult OPCs. Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS) characterized by inflammation, which leads to formation of demyelinating areas due to loss of oligodendrocytes, astrogliosis and, finally, axonal degeneration. Taken together, these results demonstrate the important role of miR-200b in modulating the MAPK pathway via c-Jun which in turn affects different aspects of the inflammatory process accompanying microglia activation including cytokine response, NO production, phagocytosis and neuronal cell death. For this purpose, coronal cryostat free-floating sections from the brain of both adult transgenic mice and their corresponding wild-type (Wt) littermates, were processed for the study of astrocytes using GFAP immunohistochemistry and microglia using antibodies against Iba1 and several markers commonly related to the activated phenotype of these microglial cells, such as CD16/32 (Fc receptor), F4/80, CD11b, CD206, CD150 and MHC-II.
cord-023935-o2ffxgnn	2011	SIRS i s a state of infl ammatory/ immune activation and is based on the presence of at least two of the four following clinical criteria: Temperature >38°C or <36°C, heart rate >90th percentile for age, respiratory rate >90th percentile for age, or hyperventilation to PaCO 2 < 32 mm Hg. The defi nition attempts to "capture" all patients at risk for the subsequent development of severe sepsis or septic shock. Among these, the nuclear factor-k B (NF-k b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. Nuclear factork B (NFk b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response.
cord-029488-l11ufs6k	2020	Expression levels of VEGF were significantly reduced in lung tissues from mice with both intranasal LPS administration and cecal ligation and puncture (CLP)-induced sepsis, which may stem from decreases in non-endothelial cells-dependent VEGF production in the lungs. In support of this assumption, stimulation with LPS and interferon-γ (IFN-γ) significantly increased VEGF in human pulmonary microvascular endothelial cells (HPMECs) at mRNA and protein levels. Taken together, our results indicate that VEGF can contribute to the development of non-cardiogenic lung edema in sepsis-associated ALI due to increased VEGF secretion from pulmonary vascular endothelial cells through multiple MAPK-dependent pathways. We thus examined whether expression of VEGF in human pulmonary microvascular endothelial cells is regulated by MAPKs. When HPMEC-ST1.6R cells were treated with PD98059, an inhibitor of MAPK kinase which is an ERK1/2 upstream activator, or SB203580, which is widely used as a specific inhibitor of p38 MAPK, the LPS/IFN-γinduced increase in VEGF protein levels was strongly blocked (Fig. 4b) .
cord-029969-1fa8hk2n	2020	Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically. Mechanism studies showed that the activation of HMGB1/TLRs/NF-κB pathway induced by LPS increased inflammatory responses and oxidative stress, while its blockade by lycorine effectively suppressed pulmonary inflammatory response and oxidative stress, and further alleviated lung injury.
cord-030385-btf502ju	2020	However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. Our results showed that females expressed higher IL-6 and TNFα than males in sepsis, and trained immunity exacerbated this trend (Figures 1I,J) . The in vitro trained immunity model was established with RAW264.7 and J774 ( Figure 5C ) cell lines derived from male and female mice, respectively.
cord-032181-gmcugd8h	2019	3. Hepatorenal syndrome, which is characterized by renal failure, hemodynamic changes in arterial circulation and abnormalities in the endogenous vascular system, is a common clinical complication of end-stage liver disease, and one of the important indicators for the prognosis of patients with severe hepatitis. The latest report indicated that basic laboratory examinations for coagulation function testing in common use at present, such as PT, APTT, international normalized ratio (INR) etc., have little correlation with occurrence of gastrointestinal bleeding in these patients, thereby revealing the importance to search and pay close attention to those complicating disease upregulating bleeding risk, such as bacterial infection, renal failure, hemodynamic change after portal hypertension, dysfunction of endotheliocyte as well as macrophagocyte and so on [107] .
cord-032564-0t5lr4z9	2020	5 We report here that LPS-related markers were associated with activated lung alveolar M2 macrophages in OT2D, with a reduction in plasma LBP as a surrogate marker of circulatory LPS elevation. Elevated plasma levels of TGF-β1, PDGF-β, MMP7 and MMP9 determined early in the course of COVID19 infection in a patient with OT2D may indicate potential risk for more severe disease. Moreover, it is also possible that, apart from alveolar macrophages, other cellular sources, for example lung epithelial cells [16] , arterial smooth muscle cells [17] , epithelial cells of glandular tissues like prostate [18] or bile duct epithelia [19] , might contribute to LPS-induced elevated plasma levels of those pro-fibrotic markers. In conclusion, in OT2D the lung epithelial barrier integrity is likely destabilized in response to fibroproliferative activity of elevated TGF-β1, PDGF-β, MMP7 or MMP9 derived from lung alveolar macrophages, increasing vulnerability to inhaled pathogens.
cord-103496-8tq78p2z	2020	title: RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury Using a molecular modeling approach, we designed a nitration shielding peptide for Rac1, designated NipR2 (nitration inhibitor peptide for the Rho GTPases 2), which attenuated the LPS-induced nitration of Rac1 at Y32, preserves Rac1 activity and attenuates the LPS-mediated disruption of the endothelial barrier in human lung microvascular endothelial cells (HLMVEC). Using a murine model of ALI induced by intratracheal installation of LPS we found that NipR2 successfully prevented Rac1 nitration and Rac1 inhibition, and more importantly attenuated pulmonary inflammation, reduced lung injury and prevented the loss of lung function. We anticipate that a successful clinical efficacy of NipR2 or similar product might require: 1) precision medicine approach to identify patients in the sub-group with satisfactory responsiveness of Rac1 nitration blockade, as not all triggers of ALI (e.g., trauma) will lead to endothelial oxidative stress and peroxynitrite generation; 2) combination therapy with other effective reagents, including suppressor of the cytokine storm and/or neutrophil eliminators; 3)
cord-103592-lkngp2u6	2020	Using cecal ligation and puncture (CLP), a reproducible and clinically relevant mouse model of polymicrobial infection that causes ALI, we found that in naïve control mice after 2 sequential i.v. injections of ANP only ~4% of lung PMN endocytosed ANP as evidenced by ANP-specific fluorescence ( Figure 1B) . Importantly, we found that CCR1 receptor cell surface expression, consistent with the mRNA data, was significantly greater on lung ANP high PMN than in ANP low PMN before and 3h, 6h, and 12h after LPS stimulation ( Figure 3B ). We observed that nitrotyrosine-specific staining in inflammatory and parenchymal cells was significantly reduced in lungs and livers of mice treated with PANP when compared to ANP-treated controls ( Figure 6D ,E). Measuring a markers of overall cell damage, lactic dehydrogenase (LDH) (34) , revealed that the polymicrobial sepsis-induced increased serum activity of LDH was significantly reduced by PANP treatment when compared to ANP treated controls ( Figure 6G ).
cord-252855-xtsnlu1f	2017	
cord-252859-zir02q69	2006	BACKGROUND: Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation. Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. 17, 18 We hypothesized that leukocyte gene expression profiles obtained using DNA microarrays could be used to predict septic states; in particular, distinguishing between sterile and infectious sources of systemic inflammation, a common conundrum in caring for the critically ill or injured. 30 PCA analysis of these 25 probe sets revealed that the seven experimental groups were clustered into three apparent phenotypes (Fig. 4) : control animals, LPS-treated animals (sterile source of systemic inflammation), and those that had any CLP treatment (Sepsis).
cord-255578-0ltb9dpa	2020	title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway Deficiency of factor H-related protein 1 (FHR-1), which is a regulator of AP, has been considered as a susceptible factor for atypical hemolytic uremic syndrome (aHUS) and other types of nephropathy when an inducer such as infection exists. We found that murine FHR-1 homolog (FHR-E) deficiency enhanced lipopolysaccharide (LPS)-induced AP activation both in vitro and in vivo and that Cfhr1 knockout mice exhibited more severe sepsis and AKI in response to LPS challenge. These results indicated that FHR-E deficiency promoted LPS-induced sepsis and AKI through AP over-activation, providing a mouse model for studying AP regulation and sepsis. In this study, Cfhr1 was deleted on C57BL/6 mouse to study the function of FHR-E on AP and the effect of FHR-E deficiency on LPS-induced sepsis.
cord-257092-r11cgpvs	2015	Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. We observed reduced neutrophil infiltration and attenuated leukocyte-endothelial cell interactions in CXCR2 −/− and CXCL1 −/− mice following the intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). To identify the source of functional CXCR2 that mediates leukocyte recruitment, we generated chimeric mice by transferring bone marrow cells between WT and (See figure on previous page.) Fig. 2 Chemokine levels and the effect of CXCR2 or CXCL1 deficiency on neutrophil recruitment to the brain parenchyma after i.c.v. LPS injection. Following stimulation with TNF-α or LPS, the cerebral endothelial cells, compared with astrocytes and microglia, also expressed much higher level of CXCR2 protein (Fig. 7D ). Our results demonstrate that CXCL1, an important factor secreted by astrocytes, also plays a critical role in leukocyte recruitment to the CNS by cooperating with CXCR2 expressed on cerebral endothelial cells.
cord-261367-i1n8x0uc	2020	Instead, mice with iBALT had reduced Th2-associated mRNA expression, less eosinophil recruitment to the lungs and airways, attenuated goblet cell hyperplasia and reduced mucus production following pulmonary sensitization and challenge with OVA. To test the effect of iBALT on the immune response to a pulmonary allergen, we administered LPS (or PBS) to neonatal mice as described above, allowed the mice to rest until they were 7 weeks old, then intranasally sensitized the iBALT and control groups with 100 µg OVA in combination with low dose (0.1 µg) LPS on days 49, 50, and 51 and challenged them on days 63, 64, 67, and 68 with 25 µg OVA ( Figure 1E ). Together, these data suggest that the spatial distribution of effector Th2 cells and Tregs is affected by the presence of iBALT (they cluster together), which may explain how iBALT and control mice can have similar numbers of Th2 cells in their lungs, but have so profoundly different outcomes in terms of eosinophil accumulation and histopathology.
cord-264145-73e61rlq	2020	The overall intestinal lipopolysaccharide (LPS) composition in the individuals with obesity could be shifted away from immunosilent/immunoinhibitory Bacteroidetes LPS subtypes, in favor of various proinflammatory LPS subtypes due to gut microbiome dysbiosis. ABSTRACT: The overall intestinal lipopolysaccharide (LPS) composition in the individuals with obesity could be shifted away from immunosilent/immunoinhibitory Bacteroidetes LPS subtypes, in favor of various proinflammatory LPS subtypes due to gut microbiome dysbiosis. Taking everything into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity. Taking everything into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity. Taking everything previously mentioned into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity (Figure 1 ).
cord-270213-ygb64yxc	2020	Given that endothelial dysfunction is a common denominator in many acute inflammatory conditions, it is likely that NO enhancement strategies may be useful for the treatment of sepsis and other acute inflammatory insults that trigger severe systemic pro-inflammatory responses and often result in a cytokine storm, as seen in COVID-19. A well-described hallmark of sepsis is endothelial dysfunction in response to a cytokine 81 ''storm'', which is associated with an increase in a series of negative consequences arising from 82 overproduction of reactive oxygen species (ROS), disruption of the glycocalyx, and endothelial 83 nitric oxide synthase (eNOS) uncoupling, all contributing to increased adhesion of red blood 84 cells (RBCs), white blood cells (WBCs), and platelets to the endothelium lining, enhanced 85 platelet activation, blood stagnation, decreased tissue perfusion and increased vascular 86 permeability. Mice treated with Control-np in our study 382 experienced significantly increased vascular permeability, as shown in Figure 4 , suggesting 383 endothelial cell and glycocalyx disruption in these animals.
cord-273594-vmbhok1u	2014	
cord-280482-o887a7q9	2016	
cord-280850-lku2g69k	2013	title: Aqueous extract of Bai-Hu-Tang, a classical Chinese herb formula, prevents excessive immune response and liver injury induced by LPS in rabbits In this study, a febrigenic dosage of LPS (15 mg/kg i.v.) was injected into rabbits to form an animal febrile model, then the model animals were gavaged with BHT at the same time, and the formula''s function of liver damage prevention and immunomodulation was researched in rabbits. Therefore, BHT did not affect the activated adaptive immunity, but prevented the cell immunity inhibition and excessive cytokines in innate immunity by LPS at the same time. The gene expressions of TLR4 studied herein were not affected by BHT (Fig. 5A ), but LBP expression was increased (Fig. 5B) , which bind and transport LPS to activate cells in the immunity system (Knapp et al., 2006) , and inhibiting inflammatory response at higher concentration (Hamann et al., 2005) .
cord-282336-zvc04s39	2020	In contrast, the lung injury in LPS-challenged TTP KO mice was characterized by severe consolidation (>90% of total area of lung section) (Figures 1F,G) that included infiltration of neutrophils, edema, fibrin, and airspace hemorrhage within the airway and alveolar lumen, multifocal loss of bronchiolar epithelium with infiltration of neutrophils and red blood cells within the bronchiolar lumen, and moderate to severe perivascular edema and inflammation (Figures 1F-H) . To determine the cell-specific role of TTP levels in ALI, we modulated TTP levels in hematopoietic progenitor cells (HPCs) and non-HPCs. In order to test whether donor HPCs repopulate the recipient mouse lungs, we first made bone marrow chimeras in which total body irradiated WT mice were transplanted with HPCs from a mouse expressing green fluorescent protein (GFP) in their somatic cells.
cord-283427-fef9qsik	2019	In our previous study, we established of minimal positive control conditions to ensure brain safety using experimental mice models during development of urgent vaccines before introducing to markets. In this study, we described that this module can be useful in applying a commercially available vaccine to a rapid and effective positive-control for brain safety assessment of an urgent vaccine. In brief, evidences for the BBB damage by commercially available vaccines (killed porcine genital respiratory syndrome vaccine vaccine and live canine parvovirus vaccine) were based on Evans blue EB permeability into brain parenchyma and mRNA expression of tight junctions (ZO-1 and Occludin) in the brain. However, when 2-fold concentrations of two vaccines stock solutions were injected, occludin mRNA expression was increased compared to the PBS group, but not significantly. In the present study, we confirmed that these established conditions and modules of the positive control that destroyed the BBB could be used to assess brain safety of commercial vaccines [1] .
cord-285684-iiqyzqsb	2020	title: Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier The aim of this study was to evaluate the potential therapeutic effects of MS-MSCs on pulmonary microvascular endothelium barrier injuries induced by LPS. These data demonstrated that the MS-MSC groups had potential therapeutic effects on the LPS-treated ECs; these results might be useful in the treatment of ARDS. We introduced a transwell coculture system to evaluate the effects of MS-MSCs on the paracellular permeability of LPS-treated ECs. Treatment with LPS significantly increased the paracellular permeabil-ity of the pulmonary microvascular endothelium barrier (Figure 6 (a); * * p < 0:01). We demonstrated that mechanical stretch could impact MSC morphology and biological function in a time-and magnitude-dependent manner and that MS-MSCs could restored the increased permeability of endothelial cells induced by LPS. In this study, we tried to discover evidences of mechanically stretched MSCs in restoring increased permeability of endothelial barrier induced by LPS.
cord-292862-ezrkg0dc	2020	
cord-294193-xjq9j2gv	2015	
cord-296258-8pc2p3az	2016	title: Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation In the present study, we investigated the role of Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF), one of the two major TLRs–adaptor molecules, on innate immune response induced by TLR3 and TLR4 stimulation in murine peritoneal mesothelial cells (PMCs). When faced with an infection, mesothelial cells express specific surface markers that enable them to promote the migration of neutrophils, to interact with extracellular matrix proteins, to present antigens to immune cells, and to produce biologically important molecules such as proinflammatory cytokines, chemokines, and nitric oxide (NO) [6, 7] Toll-like receptors (TLRs) are type I transmembrane proteins and comprise an ectodomain, which contains leucine-rich repeats that mediate the recognition of pathogen-associated molecular patterns (PAMPs); a transmembrane region; and a cytosolic Toll/ IL-1 receptor (TIR) domain that activates downstream signaling pathways [8] .
cord-297128-s5c9h4lm	2012	
cord-298224-flyx85lr	2020	Following optimization with antiglyceraldehyde 3-phosphate dehydrogenase (GAPDH) siRNA, PEI and PEI-LPEG anti-IL8 siRNA nanoparticles were assessed for efficacy using polarised Calu-3 human airway epithelial cells and a twin stage impinger (TSI) in vitro lung model. This work demonstrates the potential of nebulised PEI-PEG siRNA nanoparticles in modulating pulmonary inflammation and highlights the need to move towards more relevant in vitro and in vivo models for respiratory drug development. In contrast, the nebulised PEI-LPEG siRNA nanoparticles demonstrated significantly greater levels of GAPDH knockdown versus the PBS-treated controls at higher doses. Using the differential cell staining of BAL samples with Eosin Y and azur/methylene blue, it was In the case of the PEI-LPEG siRNA nanoparticle-treated groups, both the non-targeting (NT) and anti-CXCL-1 siRNA-treated groups demonstrated 10-fold decreases in the CXCL-1 gene expression compared to the PBS-LPS samples (4-vs.
cord-298646-wurzy88k	2012	This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD. One of the main challenges in developing new therapeutic agents for the treatment or prevention of acute exacerbations of COPD is that their potential success cannot be entirely known until the investigational therapies enter relatively large Phase II studies, assessing clinical outcome over a 3-to 6-month period or longer. 20 In the first reported study of the inflammatory effects of low-level O 3 exposure (80 ppb O 3 for 6.6 hours) in healthy volunteers, 21 there were statistically significant increases in polymorphononuclear neutrophils, prostaglandin E 2 , lactate dehydrogenase, IL-6, α1-antitrypsin, and decreased phagocytosis via the complement receptor. The O 3 -challenge model potentially provides critical decision-making data in understanding whether new compounds have the desired biological effect in healthy volunteers and patients with COPD; hence it can de-risk decisions to move forwards into large Phase II safety and efficacy trials.
cord-300912-w85t4zz6	2017	title: n-butanol extract from Folium isatidis inhibits the lipopolysaccharide-induced downregulation of CXCR1 and CXCR2 on human neutrophils Our previous study investigated the effect of n-butanol extract from Folium isatidis on lipopolysaccharide (LPS)-induced septic shock. The addition of n-butanol extract from Folium isatidis inhibited this LPS-induced downregulation of CXCR1, CXCR2 and CD62L, and decreased the expression of IL-8 on neutrophils. The isolated neutrophils were treated with either vehicle or increasing concentrations (10, 100 and 1,000 ng/ml) of LPS for 4 h, and the expression levels of CXCR1, CXCR2, TLR2, TLR4, CD11b and CD62L were measured using flow cytometry. n-butanol extract from Folium isatidis prevents the LPS-induced downregulation of CXCR1, CXCR2 and CD62L. Subsequent analysis of the cells using flow cytometry indicated that the extract inhibited the LPS-induced downregulation of CXCR1, CXCR2 and CD62L ( Fig. 2A-C) in a dose-dependent manner. Effect of n-butanol extract from Folium isatidis on the gene expression levels of CXCR1, CXCR2 and CD62L.
cord-302295-nblmshni	2013	
cord-302490-em1tiz7s	2020	
cord-306577-gq6fss5l	2002	Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. We developed a model of bowel necrosis in adult rats and mice by injecting endotoxin (lipopolysaccharide, LPS) [32] , PAF (platelet-activating factor, paf-acether) [33, 34] , tumor necrosis factor-␣ (TNF) [35] , or a combination of these agents. Experimental evidence strongly supports the role of PAF, LPS, and TNF in acute ischemic bowel necrosis and in the neonatal rat model of NEC. Hypoxia causes ischemic bowel necrosis in rats: the role of platelet-activating factor (PAF-acether)
cord-310535-ay2cdf2w	2017	title: Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium(DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E(2), nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. The effects of HMFO on the expression of inflammatory proteins such as COX-2 and iNOS in cytosolic extracts from the colon of colitis mice were detected by Western blot analysis.
cord-311481-2awvmpyh	2020	OBJECTIVE: In the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. In the present study, we hypothesized that LPZ has the potential to suppress IRF7 and NF-κB, in the same manner as BAY11-7082, and so prevent corticosteroid-induced ONFH in rats. The present study showed that the co-treatment of LPZ with corticosteroids prevents the development of ONFH in experimental animals, as well as in patients with immune disease treated with corticosteroids. The results of the experimental study indicate that LPZ may also prevent the development of ONFH in patients with immune diseases needing corticosteroid treatment. The present study shows that the co-treatment of LPZ with corticosteroids prevents the development of ONFH through the suppression of IRF7 activity in rats. Nevertheless, we believe that LPZ is safe to use and could be effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment.
cord-322729-47c9z2gk	2014	
cord-329274-ncvvmkca	2002	
cord-331887-kagggou1	2020	Compared with those in ALI, the expression of CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3, which are involved in the IL-17 signalling pathway, were significantly decreased in the LJF group according to the qRT-PCR analyses. CONCLUSIONS: In view of the network pharmacology and RNA-Seq results, the study identified the main active ingredient and potential targets of LJF involved in protecting against ALI, which suggests directions for further research on LJF. LJF significantly inhibited CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, 290 IL17F, IL17C, MMP9, and TNFAIP3 mRNA expression in lung tissue homogenates according to 291 RNA-Seq, which indicates that the IL-17 signalling pathway is critical for treatment of 292 LPS-induced ALI with LJF (Fig.S4) . Consistent with the RNA-Seq data, the expression of CXCL2, CXCL1, CXCL6, 295 NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3 in lung tissue was 296 significantly decreased compared with that in the ALI and LJF groups according to the qRT-PCR 297 analyses (P<0.05) (Fig.8) .
cord-335107-ew9uid2e	2020	
cord-336432-tu00gffr	2020	
cord-337923-1vbkttzx	2019	henryi have strong antioxidant and antiacetyl cholinesterase activities [6] , and the 80% methanol fraction of root bark and ciwujianoside C3, which was isolated from leaves of this plant, have significant antiinflammatory effect in lipopolysaccharide-(LPS-) induced RAW264.7 macrophage cells [5, 11] . henryi, we selected 13 compounds (compounds -, , , , , , , , and -) based on their number of publications, and these compounds were screened for anti-inflammatory effects, including the inhibition of NO and PGE 2 production, in LPS-stimulated BV2 microglial cells. The concentration required to inhibit the production of NO by 50% (IC 50 value) was calculated based on the concentrations of NO and PGE 2 released into the culture Figure 2 : The effect of compound on LPS-induced iNOS and COX-2 protein expression in BV2 microglial cells. henryi, suppressed NO and PGE 2 production in LPS-stimulated BV2 microglial cells and also inhibited the LPS-induced expression of the iNOS and COX-2 protein (Figure 2) .
cord-339272-trd6rkxw	2013	
cord-341458-hkopopa6	2020	
cord-342001-41vjh3mq	2020	
cord-346488-y7r7el4e	2017	
cord-348391-xytmq2f2	2020	
cord-349201-d88g5toc	2020	
cord-351310-6p42b144	2020	
cord-351730-qmbo1dmo	2020	
cord-352219-z245sb3s	2016	
cord-354765-abayh871	2020	
cord-354829-god79qzw	2020