id	author	title	date	pages	extension	mime	words	sentences	flesch	summary	cache	txt
cord-306983-6w2fvtfy	Wang, Siye	Influenza Virus—Cytokine-Protease Cycle in the Pathogenesis of Vascular Hyperpermeability in Severe Influenza	2010-10-01		.txt	text/plain	3808	223	39	Influenza A virus infection resulted in significant increases in TNF-α, IL-6, IL-1β, viral hemagglutininprocessing protease trypsin levels, and viral replication with vascular hyperpermeability in lung and brain in the first 6 days of infection. The present study reports several new observations: (1) proinflammatory cytokines, TNF-a, IL-1b, and IL-6, when upregulated by influenza A virus infection, induce trypsin expression in various organs and human endothelial cells; (2) the upregulated trypsin induces [Ca 2+ ] i mobilization via activation of the PAR-2, followed by loss of zonula occludens-1 and vascular hyperpermeability; (3) inhibitors of NF-kB and activator protein 1 effectively suppress the upregulation of proinflammatory cytokines and trypsin and improve the survival rates of infected mice. The present results allow us to propose a new mechanism of junctional permeability regulation: upregulated trypsin by influenza A virus and/or proinflammatory cytokines induces increase in [Ca 2+ ] i and loss of zonula occludens-1 in endothelial cells via PAR-2 signaling.	./cache/cord-306983-6w2fvtfy.txt	./txt/cord-306983-6w2fvtfy.txt