PMID- 17276989
OWN - NLM
STAT- MEDLINE
DCOM- 20070606
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 14
DP  - 2007 Apr 6
TI  - A novel role for the glucocorticoid receptor in the regulation of monocyte 
      chemoattractant protein-1 mRNA stability.
PG  - 10146-52
AB  - Monocyte chemoattractant protein-1 (MCP-1) plays an important role in attracting 
      monocytes to sites of inflammation and is the dominant mediator of macrophage 
      accumulation in atherosclerotic plaques. We have previously shown that 
      glucocorticoids inhibit the secretion of MCP-1 in arterial smooth muscle cells 
      (SMC) by markedly decreasing MCP-1 mRNA stability. We now report that the 
      destabilization of MCP-1 mRNA is mediated by the glucocorticoid receptor (GR). 
      The GR antagonist, RU486, blocked the effect of the glucocorticoid dexamethasone 
      (Dex) on MCP-1 mRNA stability in SMC culture. Using a previously reported in 
      vitro mRNA gel shift and stability assay, antibodies to the GR blocked the 
      ability of cytoplasmic extracts from Dex-treated SMC to decay MCP-1 mRNA. 
      Recombinant human GR (rhGR) bound in a concentration-dependent manner to in vitro 
      transcribed MCP-1 mRNA, whereas other members of the steroid hormone receptor 
      family did not. Binding of GR to MCP-1 mRNA was specific as it was not found to 
      bind other mRNAs. Immunoprecipitation of GR in extracts from Dex-treated SMC 
      followed by real-time reverse transcription-PCR demonstrated that endogenous GR 
      was bound specifically to MCP-1 mRNA. The addition of exogenous rhGR blocked the 
      ability of extracts from Dex-treated SMC to degrade MCP-1 mRNA, suggesting that 
      exogenous rhGR can compete with an endogenous GR-containing degradative complex. 
      These data suggest a novel role for the GR in binding to and facilitating mRNA 
      degradation. These results provide novel insights into GR function and may 
      provide a new approach to attenuate the inflammatory response mediated by MCP-1.
FAU - Dhawan, Latika
AU  - Dhawan L
AD  - Cardiovascular Research Institute, University of Rochester, Rochester, New York 
      14620, USA.
FAU - Liu, Bin
AU  - Liu B
FAU - Blaxall, Burns C
AU  - Blaxall BC
FAU - Taubman, Mark B
AU  - Taubman MB
LA  - eng
GR  - P01 HL77789/HL/NHLBI NIH HHS/United States
GR  - R01 HL77669/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070202
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Hormone Antagonists)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 320T6RNW1F (Mifepristone)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/pharmacology
MH  - Atherosclerosis/metabolism/pathology
MH  - Cell-Free System/metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Dexamethasone/pharmacology
MH  - Hormone Antagonists/pharmacology
MH  - Humans
MH  - Inflammation/genetics/metabolism/pathology
MH  - Male
MH  - Mifepristone/pharmacology
MH  - Muscle, Smooth, Vascular/*metabolism/pathology
MH  - Myocytes, Smooth Muscle/*metabolism/pathology
MH  - *RNA Stability/drug effects/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glucocorticoid/agonists/genetics/*metabolism
EDAT- 2007/02/06 09:00
MHDA- 2007/06/07 09:00
CRDT- 2007/02/06 09:00
PHST- 2007/02/06 09:00 [pubmed]
PHST- 2007/06/07 09:00 [medline]
PHST- 2007/02/06 09:00 [entrez]
AID - S0021-9258(19)57685-2 [pii]
AID - 10.1074/jbc.M605925200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Apr 6;282(14):10146-52. doi: 10.1074/jbc.M605925200. Epub 2007 
      Feb 2.