An ADIOL-ERbeta-CtBP transrepression pathway negatively regulates microglia-mediated inflammation.

Authors: Saijo, K  Collier, JG  Li, AC  Katzenellenbogen, JA  Glass, CK 
Citation: Saijo K, etal., Cell. 2011 May 13;145(4):584-95.
Pubmed: (View Article at PubMed) PMID:21565615
DOI: Full-text: DOI:10.1016/j.cell.2011.03.050

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.


Disease Annotations
Objects Annotated

Additional Information

CRRD Object Information
CRRD ID: 5508732
Created: 2011-10-20
Species: All species
Last Modified: 2011-10-20
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.