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001-es BibID:BIBFORM028397
Első szerző:Eaves-Pyles, Tonyia
Cím:Flagellin, a novel mediator of Salmonella-induced epithelial activation and systemic inflammation : I kappa B alpha degradation, induction of nitric oxide synthase, induction of proinflammatory mediators, and cardiovascular dysfunction / Tonyia Eaves-Pyles, Kanneganti Murthy, Lucas Liaudet, László Virág, Gary Ross, Francisco Garcia Soriano, Csaba Szabó, Andrew L. Salzman
Dátum:2001
ISSN:1550-6606
Megjegyzések:Gram-negative sepsis is mediated by the actions of proinflammatory genes induced in response to microbes and their products. We report that flagellin, the monomeric subunit of flagella, is a potent proinflammatory species released by Salmonella. Flagellin (1 microgram/ml) induces IkappaBalpha degradation, NF-kappaB nuclear translocation, and inducible NO synthase expression in cultured intestinal epithelial cells (IEC). Aflagellic Salmonella mutants do not induce NF-kappaB activation or NO production by cultured IEC. Antiserum to flagellin blocks NO production in IEC induced by medium conditioned by a variety of motile Gram-negative enteric pathogens (Escherichia coli, Salmonella muenchen, Serratia marcescens, Proteus mirabilis, and Proteus vulgaris). Flagellin, when injected systemically (approximately 10 microgram/mouse), induces systemic inflammation characterized by the systemic expression of a range of proinflammatory cytokines and chemokines and of inducible NO synthase. At higher doses (approximately 300 microgram/mouse), flagellin induces shock, characterized by hypotension, reduced vascular contractility in mice, and death. The effects of flagellin do not diminish in C3H/HeJ LPS-resistant mice, indicating that the Toll-like receptor-4 receptor is not involved in flagellin's actions. In LPS-resistant mice, i.p. injection of S. dublin flagellin or medium conditioned by wild-type S. dublin induces serum IFN-gamma and TNF-alpha, whereas medium conditioned by aflagellic mutants has no effect. Flagellin can be detected in the blood of rats with septic shock induced by live bacteria at approximately 1 microg/ml. We propose that flagellin released by Gram-negative pathogens may contribute to the inflammatory response by an LPS- and Toll-like receptor-4-independent pathway.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Immunology 166 : 2 (2001), p. 1248-1260. -
További szerzők:Murthy, Kanneganti G. Liaudet, Lucas Virág László (1965-) (biokémikus, sejtbiológus, farmakológus) Ross, Gary Soriano, Francisco Garcia Szabó Csaba (1967-) (orvos) Salzman, Andrew L.
Internet cím:Intézményi repozitóriumban (DEA) tárolt változat
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