The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in Toll-Like Receptor 5 Signaling in Epithelial Cells
The p110α and p110β Isoforms of Class I Phosphatidylinositol 3-Kinase Are Involved in Toll-Like Receptor 5 Signaling in Epithelial Cells
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DOI：
10.1155/2010/652098
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发表时间：
2010-01-01
影响因子：
4.6
通讯作者：
Steiner, Theodore S.
中科院分区：
文献类型：
--
作者：
Ivison, Sabine M.;Khan, Mohammed A. S.;Steiner, Theodore S.
背景资料。细菌鞭毛蛋白通过Toll样受体(TLR)5触发哺乳动物细胞的炎症反应。鞭毛蛋白释放的趋化因子IL-8涉及核因子-kappa B、p38 MAP激酶和磷脂酰肌醇3-激酶(PI3K)。然而，据报道，PI3K在不同的模型系统中既有促炎作用，也有抗炎作用。我们推测，这可能是由于PI3K的p110α和β亚型的不同活性所致。结果。鞭毛蛋白能迅速激活Caco-2结肠癌细胞中的PI3K和Akt。利用基于质粒的shRNA传递系统和新型p110异构体特异性抑制剂，我们发现鞭毛蛋白诱导的IL-8的产生依赖于p110α和p110β。然而，在小鼠中，抑制p110β而不是p110α可降低由腹腔注射鞭毛蛋白引起的血清IL-6水平的升高。结论。这些数据表明，在鞭毛蛋白的促炎反应中，IA类PI3K的p110a和β亚型都是必需的。
Background. Bacterial flagellin triggers inflammation in mammalian cells via Toll-like receptor (TLR) 5. Release of the chemokine IL-8 in response to flagellin involves NF-kappa B, p38 MAP kinase, and phosphatidylinositol 3-kinase (PI3K). However, PI3K has been reported to be either pro-or anti-inflammatory in different model systems. We hypothesized that this could be due to different activities of the p110 alpha and beta isoforms of PI3K. Results. PI3K and Akt were rapidly activated in Caco-2 colon carcinoma cells by flagellin. Using a plasmid-based shRNA delivery system and novel p110 isoform-specific inhibitors, we found that flagellin-induced IL-8 production was dependent on both p110 alpha and p110 beta. However in the mouse, inhibition of p110 beta but not p110 alpha reduced the increase of serum IL-6 levels induced by intraperitoneal injection of flagellin. Conclusions. These data demonstrate that the p110a and beta isoforms of class IA PI3K are both required for the proinflammatory response to flagellin.