Thu, 21 Aug 2008 00:01:19 BST CiteULike: AlfonsoVicenteSuarez's library [225 articles] http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1387643 CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/AlfonsoVicenteSuarez/article/1387643 <i>Infect. Immun., Vol. 69, No. 7. (1 July 2001), pp. 4424-4429.</i><br /><br />Flagellin from various species of gram-negative bacteria activates monocytes to produce proinflammatory cytokines. We have analyzed the pathway by which Salmonella enteritidis flagellin (FliC) activates murine and human monocyte/macrophage-like cell lines. Since lipopolysaccharide (LPS), the principal immune stimulatory component of gram-negative bacteria, is known to signal through Toll-like receptor 4 (TLR4), we tested the possibility that FliC also signals via TLR4. When murine HeNC2 cells were stimulated with LPS in the presence of a neutralizing anti-TLR4 monoclonal antibody, tumor necrosis factor alpha (TNF-[alpha]) and nitric oxide (NO) production were markedly reduced. In contrast, FliC-mediated TNF-[alpha] and NO production were minimally affected by the anti-TLR4 antibody. Furthermore, FliC, unlike LPS, stimulated TNF-[alpha] production in the TLR4 mutant cell line, GG2EE, indicating that TLR4 is not essential for FliC-mediated signaling. To test the possibility that FliC signals via another TLR, we measured FliC-mediated activation of interleukin-1 (IL-1) receptor-associated kinase (IRAK), a central component in IL-1R/TLR signaling. FliC induced IRAK activation in HeNC2 and GG2EE cells as well as in the human promonocytic cell line THP-1. IRAK activation was rapid in HeNC2 cells, with maximal activity observed after 5 min of treatment with FliC. In addition, FliC-mediated IRAK activation exhibited the same concentration dependence as was demonstrated for the induction of TNF-[alpha]. These results represent the first demonstration of IRAK activation by a purified bacterial protein and strongly suggest that a TLR distinct from TLR4 is involved in the macrophage inflammatory response to FliC. 10.1128/IAI.69.7.4424-4429.2001 Activation of Interleukin-1 Receptor-Associated Kinase by Gram-Negative Flagellin Marlena Moors Liwu Li Steven Mizel doi:10.1128/IAI.69.7.4424-4429.2001 Infect. Immun., Vol. 69, No. 7. (1 July 2001), pp. 4424-4429. 2007-06-13T15:27:22-00:00 2001 Infect. Immun. 69 7 4424 4429 tlr5-flagellin