mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages

作者：Bao, Wenlei; Wang, Yanfeng; Fu, Yuting; Jia, Xiaoyang; Li, Jiaxin; Vangan, Nyamtsengel; Bao, Lili; Hao, Huifang; Wang, Zhigang^*

来源：PLos One, 2015, 10(5): e0125910.

DOI：10.1371/journal.pone.0125910

• NF-KAPPA-B
• PROINFLAMMATORY GENE-EXPRESSION
• MAMMALIAN TARGET
• BACTERIAL FLAGELLIN
• CUTTING EDGE
• CANCER-CELLS
• ACTIVATION
• PATHWAY
• 3-KINASE
• PROLIFERATION

Bacterial flagellin triggers inflammatory responses. Phosphoinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) regulate the production of pro-and anti-inflammatory cytokines that are induced by extrinsic antigens, but the function of mTORC1 in flagellin-induced inflammatory response is unknown. The purpose of this study was to examine the role and the mechanism of PI3K/Akt/mTOR pathway in flagellin-induced cytokine expression in mouse macrophages. We observed that flagellin upregulated TNF-alpha time-and dose-dependently. Flagellin stimulated rapid (<15 min) PI3K/Akt/mTOR phosphorylation that was mediated by TLR5. Inhibition of PI3K with LY294002 and wortmannin, and of mTORC1 with rapamycin decreased flagellin-induced TNF-a and IL-6 expression and cell proliferation. The activation of NF-kappa B p65 and STAT3 was regulated by mTORC1 via degradation of I kappa B alpha and phosphorylation of STAT3 in response to flagellin, respectively. Thus, the PI3K/Akt/mTORC1 pathway regulates the innate immune response to bacterial flagellin. Rapamycin is potential therapy that can regulate host defense against pathogenic infections.

• 出版日期2015-5-5
• 单位内蒙古大学; 内蒙古医科大学