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

Détails

ID Serval
serval:BIB_3D1BC7BB5D92
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
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
Périodique
Journal of Immunology
Auteur⸱e⸱s
Eaves-Pyles  T., Murthy  K., Liaudet  L., Virag  L., Ross  G., Soriano  F. G., Szabo  C., Salzman  A. L.
ISSN
0022-1767 (Print)
Statut éditorial
Publié
Date de publication
01/2001
Volume
166
Numéro
2
Pages
1248-60
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan 15
Résumé
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.
Mots-clé
Amino Acid Sequence Animals Caco-2 Cells DNA-Binding Proteins/biosynthesis/genetics/*metabolism Enzyme Induction/genetics/immunology Flagella/immunology/metabolism Flagellin/blood/immunology/isolation & purification/*pharmacology Gene Expression Regulation/immunology Gram-Negative Bacteria/immunology Hemodynamic Processes/genetics/immunology Humans *I-kappa B Proteins Immune Sera/pharmacology Inflammation Mediators/*metabolism Intestinal Mucosa/enzymology/*immunology/metabolism/*pathology Lipopolysaccharides/pharmacology Male Mice Mice, Inbred BALB C Mice, Inbred C3H Mice, Inbred C57BL Molecular Sequence Data Nitric Oxide/biosynthesis Nitric Oxide Synthase/*biosynthesis/genetics Rats Rats, Wistar Salmonella/immunology Salmonella Infections, Animal/genetics/*immunology/pathology/physiopathology Shock, Septic/blood/immunology/microbiology/*physiopathology Tumor Cells, Cultured
Pubmed
Web of science
Création de la notice
24/01/2008 17:01
Dernière modification de la notice
20/08/2019 13:33
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