Flagellin, a Novel Mediator ofSalmonella-Induced Epithelial Activation and Systemic Inflammation: IκBα Degradation, Induction of Nitric Oxide Synthase, Induction of Proinflammatory Mediators, and Cardiovascular Dysfunction

摘要: Gram-negative sepsis is mediated by the actions of proinflammatory genes induced in response to microbes and their products. We report that flagellin, monomeric subunit flagella, a potent species released Salmonella. Flagellin (1 μg/ml) induces IκBα degradation, NF-κB nuclear translocation, inducible NO synthase expression cultured intestinal epithelial cells (IEC). Aflagellic Salmonella mutants do not induce activation or production IEC. Antiserum flagellin blocks IEC medium conditioned variety motile enteric pathogens ( Escherichia coli , muenchen Serratia marcescens Proteus mirabilis vulgaris ). Flagellin, when injected systemically (∼10 μg/mouse), systemic inflammation characterized range cytokines chemokines synthase. At higher doses (∼300 shock, hypotension, reduced vascular contractility mice, death. The effects diminish C3H/HeJ LPS-resistant indicating Toll-like receptor-4 receptor involved flagellin’s actions. In i.p. injection S. dublin wild-type serum IFN-γ TNF-α, whereas aflagellic has no effect. can be detected blood rats with septic shock live bacteria at approximately 1 μg/ml. propose may contribute inflammatory an LPS- receptor-4-independent pathway.