PMID- 20538789
OWN - NLM
STAT- MEDLINE
DCOM- 20101104
LR  - 20131121
IS  - 1479-6813 (Electronic)
IS  - 0952-5041 (Linking)
VI  - 45
IP  - 2
DP  - 2010 Aug
TI  - 17beta-estradiol down-regulates lipopolysaccharide-induced MCP-1 production and 
      cell migration in vascular smooth muscle cells.
PG  - 87-97
LID - 10.1677/JME-09-0166 [doi]
AB  - Atherosclerosis is an inflammatory disease where lipopolysaccharide (LPS) 
      triggers the release of inflammatory cytokines that accelerate its initiation and 
      progression. Estrogen has been proven to be vasoprotective against 
      atherosclerosis; however, the anti-inflammatory function of estrogen in the 
      vascular system remains obscure. In this study, we investigated the effect of 
      estrogen on LPS-induced monocyte chemoattractant protein-1 (MCP-1; listed as CCL2 
      in the MGI database) production in vascular smooth muscle cells (VSMCs). LPS 
      significantly enhances MCP-1 production and this is dependent on nuclear factor 
      kappa B (NFkappaB) signaling, since the use of NFkappaB inhibitor pyrrolidine 
      dithiocarbamate or the silencing of NFkappaB subunit p65 expression with specific 
      siRNA largely impairs LPS-enhanced MCP-1 production. On the contrary, 
      17beta-estradiol (E(2)) inhibits LPS-induced MCP-1 production in a time- and 
      dose-dependent manner, which is related to the suppression of p65 translocation 
      to nucleus. Furthermore, p38 MAPK is rapidly activated in response to LPS, while 
      E(2) markedly inhibits p38 MAPK activation. Transfection with p38 MAPK siRNA or 
      the use of p38 MAPK inhibitor SB203580 markedly attenuates LPS-stimulated p65 
      translocation to nucleus and MCP-1 production, suggesting that E(2) suppresses 
      NFkappaB signaling by the inactivation of p38 MAPK signaling. LPS promotes VSMCs 
      migration and this is abrogated by MCP-1 antibody, implying that MCP-1 may play a 
      major role as an autocrine factor in atherosclerosis. In addition, E(2) inhibits 
      LPS-promoted cell migration by downregulation of MCP-1 production. Overall, our 
      results demonstrate that E(2) exerts anti-inflammatory property antagonistic to 
      LPS in VSMCs by reducing MCP-1 production, and this effect is related to the 
      inhibition of p38 MAPK/NFkappaB cascade.
FAU - Jiang, Ping
AU  - Jiang P
AD  - Department of Physiology, Zhongshan School of Medicine, Sun Yat-sen University, 
      Guangdong, Guangzhou 510089, People's Republic of China.
FAU - Xu, Jinwen
AU  - Xu J
FAU - Zheng, Shuhui
AU  - Zheng S
FAU - Huang, Jinghe
AU  - Huang J
FAU - Xiang, Qiuling
AU  - Xiang Q
FAU - Fu, Xiaodong
AU  - Fu X
FAU - Wang, Tinghuai
AU  - Wang T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100610
PL  - England
TA  - J Mol Endocrinol
JT  - Journal of molecular endocrinology
JID - 8902617
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Small Interfering)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cell Movement/*drug effects
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Down-Regulation/drug effects
MH  - Estradiol/*pharmacology
MH  - Female
MH  - Lipopolysaccharides/*pharmacology
MH  - Muscle, Smooth, Vascular/*cytology
MH  - Myocytes, Smooth Muscle/cytology/*drug effects/*physiology
MH  - NF-kappa B/metabolism
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction/drug effects
MH  - p38 Mitogen-Activated Protein Kinases/genetics/metabolism
EDAT- 2010/06/12 06:00
MHDA- 2010/11/05 06:00
CRDT- 2010/06/12 06:00
PHST- 2010/06/12 06:00 [entrez]
PHST- 2010/06/12 06:00 [pubmed]
PHST- 2010/11/05 06:00 [medline]
AID - JME-09-0166 [pii]
AID - 10.1677/JME-09-0166 [doi]
PST - ppublish
SO  - J Mol Endocrinol. 2010 Aug;45(2):87-97. doi: 10.1677/JME-09-0166. Epub 2010 Jun 
      10.