PMID- 27593484
OWN - NLM
STAT- MEDLINE
DCOM- 20170718
LR  - 20211204
IS  - 2042-0226 (Electronic)
IS  - 1672-7681 (Print)
IS  - 1672-7681 (Linking)
VI  - 13
IP  - 5
DP  - 2016 Sep
TI  - TSC1 controls IL-1beta expression in macrophages via mTORC1-dependent C/EBPbeta 
      pathway.
PG  - 640-50
LID - 10.1038/cmi.2015.43 [doi]
AB  - The tuberous sclerosis complex 1 (TSC1) is a tumor suppressor that inhibits the 
      mammalian target of rapamycin (mTOR), which serves as a key regulator of 
      inflammatory responses after bacterial stimulation in monocytes, macrophages, and 
      primary dendritic cells. Previous studies have shown that TSC1 knockout (KO) 
      macrophages produced increased inflammatory responses including tumor necrosis 
      factor-alpha (TNF-alpha) and IL-12 to pro-inflammatory stimuli, but whether and how TSC1 
      regulates pro-IL-1beta expression remains unclear. Here using a mouse model in which 
      myeloid lineage-specific deletion of TSC1 leads to constitutive mTORC1 
      activation, we found that TSC1 deficiency resulted in impaired expression of 
      pro-IL-1beta in macrophages following lipopolysaccharide stimulation. Such decreased 
      pro-IL-1beta expression in TSC1 KO macrophages was rescued by reducing mTORC1 
      activity with rapamycin or deletion of mTOR. Rictor deficiency has no detectable 
      effect on pro-IL-1beta synthesis, suggesting that TSC1 positively controls pro-IL-1beta 
      expression through mTORC1 pathway. Moreover, mechanism studies suggest that 
      mTORC1-mediated downregulation of the CCAAT enhancer-binding protein (C/EBPbeta) 
      critically contributes to the defective pro-IL-1beta expression. Overall, these 
      findings highlight a critical role of TSC1 in regulating innate immunity by 
      control of the mTOR1-C/EBPbeta pathway.
FAU - Yang, Tao
AU  - Yang T
AD  - State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of 
      Zoology, Chinese Academy of Sciences, Beijing, China.
FAU - Zhu, Linnan
AU  - Zhu L
AD  - State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of 
      Zoology, Chinese Academy of Sciences, Beijing, China.
FAU - Zhai, Yanhua
AU  - Zhai Y
AD  - Division of Molecular Embryonic Development, State Key Laboratory of Reproductive 
      Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
FAU - Zhao, Qingjie
AU  - Zhao Q
AD  - School of Life Science, University of Chinese Academy of Sciences, Beijing, 
      China.
FAU - Peng, Jianxia
AU  - Peng J
AD  - State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of 
      Zoology, Chinese Academy of Sciences, Beijing, China.
FAU - Zhang, Hongbing
AU  - Zhang H
AD  - Department of Physiology and Pathophysiology, National Laboratory of Medical 
      Molecular Biology, Institute of Basic Medical Sciences and School of Basic 
      Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, 
      Beijing, China.
FAU - Yang, Zhongzhou
AU  - Yang Z
AD  - MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research 
      Center, Nanjing University, Nanjing, China.
FAU - Zhang, Lianfeng
AU  - Zhang L
AD  - Key Laboratory of Human Diseases Comparative Medicine, Ministry of Health; 
      Institute of Laboratory Animal Science, CAMS & PUMC, Beijing, China.
FAU - Ding, Wenjun
AU  - Ding W
AD  - School of Life Science, University of Chinese Academy of Sciences, Beijing, 
      China.
FAU - Zhao, Yong
AU  - Zhao Y
AD  - State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of 
      Zoology, Chinese Academy of Sciences, Beijing, China.
LA  - eng
PT  - Journal Article
DEP - 20150525
PL  - China
TA  - Cell Mol Immunol
JT  - Cellular & molecular immunology
JID - 101242872
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (NF-kappa B)
RN  - 0 (TSC1 protein, human)
RN  - 0 (Tsc1 protein, mouse)
RN  - 0 (Tuberous Sclerosis Complex 1 Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - CCAAT-Enhancer-Binding Protein-beta/*metabolism
MH  - Enzyme Activation
MH  - Interleukin-1beta/*metabolism
MH  - Macrophages/*metabolism
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice, Knockout
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Models, Biological
MH  - Multiprotein Complexes/*metabolism
MH  - NF-kappa B/metabolism
MH  - *Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Tuberous Sclerosis Complex 1 Protein
MH  - Tumor Suppressor Proteins/deficiency/*metabolism
PMC - PMC5037279
EDAT- 2016/09/07 06:00
MHDA- 2017/07/19 06:00
PMCR- 2016/09/01
CRDT- 2016/09/06 06:00
PHST- 2014/08/03 00:00 [received]
PHST- 2015/04/23 00:00 [revised]
PHST- 2015/04/23 00:00 [accepted]
PHST- 2016/09/06 06:00 [entrez]
PHST- 2016/09/07 06:00 [pubmed]
PHST- 2017/07/19 06:00 [medline]
PHST- 2016/09/01 00:00 [pmc-release]
AID - cmi201543 [pii]
AID - 10.1038/cmi.2015.43 [doi]
PST - ppublish
SO  - Cell Mol Immunol. 2016 Sep;13(5):640-50. doi: 10.1038/cmi.2015.43. Epub 2015 May 
      25.