mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages.

mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages.
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mTORC1 调节巨噬细胞中鞭毛蛋白诱导的炎症反应

DOI:
10.1371/journal.pone.0125910
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Wang Z
Wang Z
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Bao W;Wang Y;Fu Y;Jia X;Li J;Vangan N;Bao L;Hao H;Wang Z

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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-α 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-α and IL-6 expression and cell proliferation. The activation of NF-κB p65 and STAT3 was regulated by mTORC1 via degradation of IκBα 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.
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