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
Details
Serval ID
serval:BIB_3D1BC7BB5D92
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
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
Journal
Journal of Immunology
ISSN
0022-1767 (Print)
Publication state
Published
Issued date
01/2001
Volume
166
Number
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
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan 15
Abstract
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.
Keywords
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
Create date
24/01/2008 17:01
Last modification date
20/08/2019 13:33