Molecular & Human Genetics Division, Indian Institute of Chemical Biology, Kolkata-700 032, India.
Can J Microbiol. 2009 Nov;55(11):1310-8. doi: 10.1139/w09-093.
Vibrio cholerae activates proinflammatory response in cultured intestinal epithelial cells. In this study, we demonstrate that V. cholerae O395 infection of intestinal epithelial cells results in the activation of Akt. Inhibition of Akt significantly decreases IL-1alpha, IL-6, and TNF-alpha production in V. cholerae infected Int407 cells. Analysis of the mechanisms of Akt influences on cytokine response demonstrates that Akt promotes NF-kappaB activation. We have extended these findings to show that Akt activation may be regulated by bacterial genes associated with virulence, adherence, or motility. Insertion mutants in the virulence genes coding for CtxA, ToxT, and OmpU of V. cholerae modulate the activation of PI3K/Akt signaling pathway, whereas an aflagellate non-motile mutant (O395FLAN) and a adherent and less motile mutant (O395Y3N/O395Y4N) of V. cholerae both show very significant down-regulation of Akt activity in Int407 cells. Together, these observations indicate that Akt promotes proinflammatory cytokine production by V. cholerae infected human intestinal epithelial cells through its influences on NF-kappaB.
霍乱弧菌激活培养肠上皮细胞中的促炎反应。在这项研究中，我们证明霍乱弧菌 O395 感染肠上皮细胞会导致 Akt 的激活。Akt 的抑制显著降低了霍乱弧菌感染的 Int407 细胞中 IL-1alpha、IL-6 和 TNF-alpha 的产生。对 Akt 影响细胞因子反应机制的分析表明，Akt 促进 NF-kappaB 的激活。我们将这些发现扩展到表明 Akt 的激活可能受到与毒力、粘附或运动相关的细菌基因的调节。霍乱弧菌编码CtxA、ToxT 和 OmpU 的毒力基因的插入突变体调节 PI3K/Akt 信号通路的激活，而霍乱弧菌的无鞭毛非运动突变体（O395FLAN）和粘附性和运动性降低的突变体（O395Y3N/O395Y4N）均显示 Akt 在 Int407 细胞中的活性受到显著下调。总之，这些观察结果表明，Akt 通过对 NF-kappaB 的影响，促进霍乱弧菌感染的人肠上皮细胞中促炎细胞因子的产生。
