Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network

Jerome C. Nwachukwu, Sathish Srinivasan, Nelson E. Bruno, Alex A. Parent, Travis S. Hughes, Julie A. Pollock, Olsi Gjyshi, Valerie Cavett, Jason Nowak, Ruben D. Garcia-Ordonez, René Houtman, Patrick R. Griffin, Douglas J. Kojetin, John A. Katzenellenbogen, Michael D. Conkright, Kendall W. Nettles

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbere02057
JournaleLife
Volume2014
Issue number3
DOIs
StatePublished - Apr 25 2014

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