TY - JOUR
T1 - Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network
AU - Nwachukwu, Jerome C.
AU - Srinivasan, Sathish
AU - Bruno, Nelson E.
AU - Parent, Alex A.
AU - Hughes, Travis S.
AU - Pollock, Julie A.
AU - Gjyshi, Olsi
AU - Cavett, Valerie
AU - Nowak, Jason
AU - Garcia-Ordonez, Ruben D.
AU - Houtman, René
AU - Griffin, Patrick R.
AU - Kojetin, Douglas J.
AU - Katzenellenbogen, John A.
AU - Conkright, Michael D.
AU - Nettles, Kendall W.
PY - 2014/4/25
Y1 - 2014/4/25
N2 - Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. Here we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERα ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFα genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERα and several ERα coregulators, suggesting that ERα functions as a primary conduit for resveratrol activity.
AB - Resveratrol has beneficial effects on aging, inflammation and metabolism, which are thought to result from activation of the lysine deacetylase, sirtuin 1 (SIRT1), the cAMP pathway, or AMP-activated protein kinase. Here we report that resveratrol acts as a pathway-selective estrogen receptor-α (ERα) ligand to modulate the inflammatory response but not cell proliferation. A crystal structure of the ERα ligand-binding domain (LBD) as a complex with resveratrol revealed a unique perturbation of the coactivator-binding surface, consistent with an altered coregulator recruitment profile. Gene expression analyses revealed significant overlap of TNFα genes modulated by resveratrol and estradiol. Furthermore, the ability of resveratrol to suppress interleukin-6 transcription was shown to require ERα and several ERα coregulators, suggesting that ERα functions as a primary conduit for resveratrol activity.
UR - http://www.scopus.com/inward/record.url?scp=84899621303&partnerID=8YFLogxK
U2 - 10.7554/eLife.02057
DO - 10.7554/eLife.02057
M3 - Article
C2 - 24771768
AN - SCOPUS:84899621303
SN - 2050-084X
VL - 2014
JO - eLife
JF - eLife
IS - 3
M1 - e02057
ER -