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mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages.
- 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.
- Subjects :
- Animals
Cell Line
Cell Proliferation drug effects
Cell Survival
Chromones pharmacology
Cytokines metabolism
Dose-Response Relationship, Drug
Flagellin pharmacology
Gene Expression Regulation
Inflammation genetics
Inflammation immunology
MAP Kinase Signaling System drug effects
Macrophages drug effects
Macrophages immunology
Macrophages, Peritoneal drug effects
Macrophages, Peritoneal immunology
Macrophages, Peritoneal metabolism
Mechanistic Target of Rapamycin Complex 1
Mice
Morpholines pharmacology
NF-kappa B metabolism
Phosphoinositide-3 Kinase Inhibitors
Proto-Oncogene Proteins c-akt metabolism
STAT3 Transcription Factor metabolism
Signal Transduction drug effects
Toll-Like Receptor 5 antagonists & inhibitors
Toll-Like Receptor 5 metabolism
Tumor Necrosis Factor-alpha metabolism
Flagellin metabolism
Inflammation metabolism
Macrophages metabolism
Multiprotein Complexes metabolism
TOR Serine-Threonine Kinases metabolism
Subjects
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