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mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages.

Authors :
Bao W
Wang Y
Fu Y
Jia X
Li J
Vangan N
Bao L
Hao H
Wang Z
Source :
PloS one [PLoS One] 2015 May 05; Vol. 10 (5), pp. e0125910. Date of Electronic Publication: 2015 May 05 (Print Publication: 2015).
Publication Year :
2015

Abstract

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.

Details

Language :
English
ISSN :
1932-6203
Volume :
10
Issue :
5
Database :
MEDLINE
Journal :
PloS one
Publication Type :
Academic Journal
Accession number :
25942007
Full Text :
https://doi.org/10.1371/journal.pone.0125910