Our recent study demonstrated that a phosphatidylinositol-3 kinase (PI3K)/Akt-dependent anti-inflammatory pathway was activated by Salmonella in intestinal epithelial cells. Salmonella virulence is dependent on the ability of the bacterium to invade nonphagocytic host cells and then survive and replicate within modified Salmonella-containing vacuoles where cholesterol accumulates. In addition, cholesterol in membrane lipid rafts is frequently a platform for the activation of downstream signaling pathways, including the PI3K/Akt pathway. However, the role of plasma membrane cholesterol in the Salmonella-induced anti-inflammatory response in intestinal epithelial cells has not been elucidated. Here, we show that the effect of plasma membrane cholesterol depletion on the inhibition of Akt activation allows sustained ERK activation and the subsequent upregulation of IL-8 expression. These results demonstrate that plasma membrane cholesterol plays a critical role in the PI3K-dependent anti-inflammatory pathway activated by Salmonella in intestinal epithelial cells.

中文翻译：

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质膜胆固醇在沙门氏菌诱导的肠上皮细胞抗炎反应中起关键作用。

我们最近的研究表明，沙门氏菌在肠上皮细胞中激活了磷脂酰肌醇3激酶（PI3K）/ Akt依赖性抗炎途径。沙门氏菌的毒力取决于细菌入侵非吞噬宿主细胞的能力，然后在胆固醇积累的改良的含沙门氏菌的液泡中存活并复制。此外，膜脂质筏中的胆固醇通常是激活下游信号传导途径（包括PI3K / Akt途径）的平台。然而，尚未阐明质膜胆固醇在沙门氏菌诱导的肠上皮细胞抗炎反应中的作用。这里，我们表明，质膜胆固醇耗竭对抑制Akt激活的作用允许持续的ERK激活和随后的IL-8表达上调。这些结果证明质膜胆固醇在肠上皮细胞中由沙门氏菌激活的PI3K依赖性抗炎途径中起关键作用。