PMID- 25942007
OWN - NLM
STAT- MEDLINE
DCOM- 20160202
LR  - 20211203
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 10
IP  - 5
DP  - 2015
TI  - mTORC1 Regulates Flagellin-Induced Inflammatory Response in Macrophages.
PG  - e0125910
LID - 10.1371/journal.pone.0125910 [doi]
LID - e0125910
AB  - 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-alpha and IL-6 expression and cell 
      proliferation. The activation of NF-kappaB p65 and STAT3 was regulated by mTORC1 via 
      degradation of IkappaBalpha 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.
FAU - Bao, Wenlei
AU  - Bao W
AD  - College of Life Science, Inner Mongolia University, Hohhot, China.
FAU - Wang, Yanfeng
AU  - Wang Y
AD  - College of Life Science, Inner Mongolia University, Hohhot, China.
FAU - Fu, Yuting
AU  - Fu Y
AD  - College of Life Science, Inner Mongolia University, Hohhot, China.
FAU - Jia, Xiaoyang
AU  - Jia X
AD  - College of Life Science, Inner Mongolia University, Hohhot, China.
FAU - Li, Jiaxin
AU  - Li J
AD  - College of Life Science, Inner Mongolia University, Hohhot, China.
FAU - Vangan, Nyamtsengel
AU  - Vangan N
AD  - College of Life Science, Inner Mongolia University, Hohhot, China.
FAU - Bao, Lili
AU  - Bao L
AD  - College of Life Science, Inner Mongolia University, Hohhot, China; College of 
      Basic Medical Science, Inner Mongolia Medical University, Hohhot, China.
FAU - Hao, Huifang
AU  - Hao H
AD  - College of Life Science, Inner Mongolia University, Hohhot, China.
FAU - Wang, Zhigang
AU  - Wang Z
AD  - College of Life Science, Inner Mongolia University, Hohhot, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150505
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Chromones)
RN  - 0 (Cytokines)
RN  - 0 (Morpholines)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (NF-kappa B)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Toll-Like Receptor 5)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 12777-81-0 (Flagellin)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Proliferation/drug effects
MH  - Cell Survival
MH  - Chromones/pharmacology
MH  - Cytokines/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Flagellin/*metabolism/pharmacology
MH  - Gene Expression Regulation
MH  - Inflammation/genetics/immunology/*metabolism
MH  - MAP Kinase Signaling System/drug effects
MH  - Macrophages/drug effects/immunology/*metabolism
MH  - Macrophages, Peritoneal/drug effects/immunology/metabolism
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Morpholines/pharmacology
MH  - Multiprotein Complexes/*metabolism
MH  - NF-kappa B/metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - STAT3 Transcription Factor/metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Toll-Like Receptor 5/antagonists & inhibitors/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
PMC - PMC4420466
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2015/05/06 06:00
MHDA- 2016/02/03 06:00
PMCR- 2015/05/05
CRDT- 2015/05/06 06:00
PHST- 2014/11/16 00:00 [received]
PHST- 2015/03/25 00:00 [accepted]
PHST- 2015/05/06 06:00 [entrez]
PHST- 2015/05/06 06:00 [pubmed]
PHST- 2016/02/03 06:00 [medline]
PHST- 2015/05/05 00:00 [pmc-release]
AID - PONE-D-14-51485 [pii]
AID - 10.1371/journal.pone.0125910 [doi]
PST - epublish
SO  - PLoS One. 2015 May 5;10(5):e0125910. doi: 10.1371/journal.pone.0125910. 
      eCollection 2015.