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Elife. 2014 Apr 25;3:e02057. doi: 10.7554/eLife.02057.

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

Author information

  • 1Department of Cancer Biology, The Scripps Research Institute, Jupiter, United States.
  • 2Department of Chemistry, University of Illinois, Urbana, United States.
  • 3Department of Molecular Therapeutics, The Scripps Research Institute, Jupiter, United States.
  • 4Nuclear Receptor Group, PamGene International, Den Bosch, Netherlands.
  • 5Department of Cancer Biology, The Scripps Research Institute, Jupiter, United States


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. In this study, 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.DOI:

Copyright © 2014, Nwachukwu et al.


estrogen receptor; inflammation; resveratrol; transcription regulation; x-ray crystallography

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