PMID- 21565615
OWN - NLM
STAT- MEDLINE
DCOM- 20110722
LR  - 20220310
IS  - 1097-4172 (Electronic)
IS  - 0092-8674 (Print)
IS  - 0092-8674 (Linking)
VI  - 145
IP  - 4
DP  - 2011 May 13
TI  - An ADIOL-ERbeta-CtBP transrepression pathway negatively regulates microglia-mediated 
      inflammation.
PG  - 584-95
LID - 10.1016/j.cell.2011.03.050 [doi]
AB  - Microglia and astrocytes play essential roles in the maintenance of homeostasis 
      within the central nervous system, but mechanisms that control the magnitude and 
      duration of responses to infection and injury remain poorly understood. Here, we 
      provide evidence that 5-androsten-3beta,17beta-diol (ADIOL) functions as a selective 
      modulator of estrogen receptor (ER)beta to suppress inflammatory responses of 
      microglia and astrocytes. ADIOL and a subset of synthetic ERbeta-specific ligands, 
      but not 17beta-estradiol, mediate recruitment of CtBP corepressor complexes to 
      AP-1-dependent promoters, thereby repressing genes that amplify inflammatory 
      responses and activate Th17 T cells. Reduction of ADIOL or ERbeta expression results 
      in exaggerated inflammatory responses to TLR4 agonists. Conversely, the 
      administration of ADIOL or synthetic ERbeta-specific ligands that promote CtBP 
      recruitment prevents experimental autoimmune encephalomyelitis in an 
      ERbeta-dependent manner. These findings provide evidence for an 
      ADIOL/ERbeta/CtBP-transrepression pathway that regulates inflammatory responses in 
      microglia and can be targeted by selective ERbeta modulators.
CI  - Copyright (c) 2011 Elsevier Inc. All rights reserved.
FAU - Saijo, Kaoru
AU  - Saijo K
AD  - Department of Cellular and Molecular Medicine, School of Medicine, University of 
      California, San Diego, 9500 Gilman Dr., La Jolla, CA 92093, USA.
FAU - Collier, Jana G
AU  - Collier JG
FAU - Li, Andrew C
AU  - Li AC
FAU - Katzenellenbogen, John A
AU  - Katzenellenbogen JA
FAU - Glass, Christopher K
AU  - Glass CK
LA  - eng
GR  - DK015556/DK/NIDDK NIH HHS/United States
GR  - R37 DK015556/DK/NIDDK NIH HHS/United States
GR  - R01 CA052599-20/CA/NCI NIH HHS/United States
GR  - R37 DK015556-39/DK/NIDDK NIH HHS/United States
GR  - R01 DK015556/DK/NIDDK NIH HHS/United States
GR  - R01 HL087391/HL/NHLBI NIH HHS/United States
GR  - R01 CA052599-18/CA/NCI NIH HHS/United States
GR  - HL087391/HL/NHLBI NIH HHS/United States
GR  - R01 CA052599-19/CA/NCI NIH HHS/United States
GR  - R01 CA052599/CA/NCI NIH HHS/United States
GR  - R01 DK091183/DK/NIDDK NIH HHS/United States
GR  - R01 HL087391-05/HL/NHLBI NIH HHS/United States
GR  - CA52599/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cell
JT  - Cell
JID - 0413066
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 95PS51EMXY (Androstenediol)
RN  - EC 1.1.- (17-Hydroxysteroid Dehydrogenases)
RN  - EC 1.1.- (Alcohol Oxidoreductases)
RN  - EC 1.1.1.- (C-terminal binding protein)
SB  - IM
CIN - Cell. 2011 May 13;145(4):495-7. PMID: 21565607
CIN - Nat Rev Neurol. 2011 Jul;7(7):355. PMID: 21691333
CIN - Nat Rev Drug Discov. 2011 Jul;10(7):492. PMID: 21720401
MH  - 17-Hydroxysteroid Dehydrogenases/metabolism
MH  - Alcohol Oxidoreductases/metabolism
MH  - Androstenediol/metabolism
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Cells, Cultured
MH  - DNA-Binding Proteins/metabolism
MH  - Encephalomyelitis, Autoimmune, Experimental/*metabolism/prevention & control
MH  - Estrogen Receptor beta/*metabolism
MH  - Humans
MH  - Inflammation/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*metabolism
MH  - Neurodegenerative Diseases/metabolism
MH  - Proto-Oncogene Proteins c-fos/metabolism
MH  - *Signal Transduction
PMC - PMC3433492
MID - NIHMS290587
COIS- Conflicts of interest None
EDAT- 2011/05/14 06:00
MHDA- 2011/07/23 06:00
PMCR- 2012/09/04
CRDT- 2011/05/14 06:00
PHST- 2010/09/17 00:00 [received]
PHST- 2011/02/22 00:00 [revised]
PHST- 2011/03/28 00:00 [accepted]
PHST- 2011/05/14 06:00 [entrez]
PHST- 2011/05/14 06:00 [pubmed]
PHST- 2011/07/23 06:00 [medline]
PHST- 2012/09/04 00:00 [pmc-release]
AID - S0092-8674(11)00427-2 [pii]
AID - 10.1016/j.cell.2011.03.050 [doi]
PST - ppublish
SO  - Cell. 2011 May 13;145(4):584-95. doi: 10.1016/j.cell.2011.03.050.