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
中科院分区:
文献类型:
--
作者:
Bao W;Wang Y;Fu Y;Jia X;Li J;Vangan N;Bao L;Hao H;Wang Z
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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DOI:
10.1084/jem.20092253
发表时间:
2010-06-07
期刊:
The Journal of experimental medicine
影响因子:
--
作者:
Feng T;Wang L;Schoeb TR;Elson CO;Cong Y
通讯作者:
Cong Y
影响因子:
15.9
作者:
Gewirtz, AT;Rao, AS;Neish, AS
通讯作者:
Neish, AS
影响因子:
30.5
作者:
Fukao, T;Tanabe, M;Koyasu, S
通讯作者:
Koyasu, S
影响因子:
30.5
作者:
Arbibe, L;Mira, JP;Knaus, UG
通讯作者:
Knaus, UG
影响因子:
30.5
作者:
Franchi, Luigi;Amer, Amal;Nunez, Gabriel
通讯作者:
Nunez, Gabriel