IL-1β expression in Int407 is induced by flagellin of Vibrio cholerae through TLR5 mediated pathway

被引:23
作者
Bandyopadhaya, Arunava [1 ]
Sarkar, Madhubanti [1 ]
Chaudhuri, Keya [1 ]
机构
[1] Indian Inst Chem Biol, Mol & Human Genet Div, Kolkata 700032, India
关键词
Vibrio cholerae; IL-1; beta; Flagellin; Int407; TLR5; NF-kappa B; MAP kinase;
D O I
10.1016/j.micpath.2008.01.004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Vibrio cholerae, a noninvasive enteric bacterium, causing inflammatory diarrheal disease cholera. is associated with the secretion of proinflamammatory cytokines including IL-1 beta ill Cultured epithelial cells. Incubation of Int407 with live V. cholerae resulted in increased IL-1 beta mRNA expression as early as 2h of infection, reached a peak at similar to 3.5 h and decreased thereafter. The identity of the effector molecule(s) is large unknown. The bacterial culture supernatant showed IL-1 beta stimulating activity. An engineered aflagellate V. cholerae flaA mutant (O395FLAN) resulted in highly reduced level of IL-1 beta; expression in Int407. The crude flagellar protein of V. cholerae as well as recombinant FlaA induced IL-1 beta expression in Int407. Infection of Toll-like receptor 5 (TLR5) transfected HeLa cells with O395FLAN showed reduced expression of IL-1 beta; compared to wild-type. Unlike wild-type V. cholerae, O395FLAN did not activate the NF-kappa B while the recombinant Ha elfin Could activate NF-kappa B. Finally. the mitogen activated protein kinases(ERK1 and 2. p38) were phosphorylated in wild-type and recombinant flagellin treated Int407 cells and inhibition of the p38 and ERK pathways significantly decreased the IL-1 beta response induced by wild-type V. cholerae as well as recombinant flagellin. Our data clearly indicate that flagellin of V. cholerae could induce IL-1 beta expression by recognizing TLR5 that activate NF-kappa B and MAP kinase in Int407. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:524 / 536
页数:13
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