PMID- 22015781
OWN - NLM
STAT- MEDLINE
DCOM- 20120315
LR  - 20211203
IS  - 1745-7270 (Electronic)
IS  - 1672-9145 (Linking)
VI  - 43
IP  - 12
DP  - 2011 Dec
TI  - Toll-like receptor 4 is up-regulated by mTOR activation during THP-1 macrophage 
      foam cells formation.
PG  - 940-7
LID - 10.1093/abbs/gmr093 [doi]
AB  - Macrophage foam cells formation is the most important process in atherosclerotic 
      plaque formation and development. Toll-like receptor 4 (TLR4) is one of the 
      important innate immune sensors of endogenous damage signals and crucial for 
      regulating inflammation. Growing evidence indicates that TLR4 plays a very 
      important role in macrophage foam cells formation. However, the underlying 
      mechanisms regulating TLR4 expression in macrophage are not fully understood. In 
      this study, we induced THP-1 macrophage foam cells formation with oxidative 
      modified low-density lipoprotein (ox-LDL). We observed that TLR4 mRNA and protein 
      expression were markedly up-regulated, and the phosphorylation of mammalian 
      target of rapamycin (mTOR) and its downstream target p70S6K were promoted during 
      foam cells formation. The mTOR inhibitor rapamycin blocked mTOR phosphorylation 
      and inhibited TLR4 expression induced by ox-LDL. Silencing mTOR, rictor or raptor 
      protein expression by small interfering RNA, also inhibited the up-regulation of 
      TLR4 expression, respectively. Inhibition of mTOR with rapamycin reversed the 
      down-regulation of cellular lipid efflux mediator ABCA1, which resulted from the 
      activation of TLR4 by ligands. These data suggested that TRL4 expression was 
      up-regulated by a mechanism dependent on mTOR signal pathway activation during 
      THP-1 macrophage foam cells formation. Inhibition of ox-LDL induced mTOR 
      activation reduced TLR4 expression, and improved the impaired lipid efflux.
FAU - Yu, Miao
AU  - Yu M
AD  - Key laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, 
      Peking Union Medical College Hospital, Peking Union Medical College, Chinese 
      Academy of Medical Sciences, Beijing, China.
FAU - Kang, Xiaomin
AU  - Kang X
FAU - Xue, Hong
AU  - Xue H
FAU - Yin, Hongchao
AU  - Yin H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111019
PL  - China
TA  - Acta Biochim Biophys Sin (Shanghai)
JT  - Acta biochimica et biophysica Sinica
JID - 101206716
RN  - 0 (ABCA1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (RICTOR protein, human)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (RPTOR protein, human)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (Regulatory-Associated Protein of mTOR)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - ATP Binding Cassette Transporter 1
MH  - ATP-Binding Cassette Transporters/metabolism
MH  - Adaptor Proteins, Signal Transducing/genetics/*metabolism
MH  - Atherosclerosis/pathology
MH  - Carrier Proteins/genetics/*metabolism
MH  - Enzyme Activation
MH  - Foam Cells/*cytology/*metabolism
MH  - Humans
MH  - Phosphorylation
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Regulatory-Associated Protein of mTOR
MH  - Ribosomal Protein S6 Kinases, 70-kDa/*metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - Toll-Like Receptor 4/*metabolism
MH  - Up-Regulation
EDAT- 2011/10/22 06:00
MHDA- 2012/03/16 06:00
CRDT- 2011/10/22 06:00
PHST- 2011/10/22 06:00 [entrez]
PHST- 2011/10/22 06:00 [pubmed]
PHST- 2012/03/16 06:00 [medline]
AID - gmr093 [pii]
AID - 10.1093/abbs/gmr093 [doi]
PST - ppublish
SO  - Acta Biochim Biophys Sin (Shanghai). 2011 Dec;43(12):940-7. doi: 
      10.1093/abbs/gmr093. Epub 2011 Oct 19.