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

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.

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Author details

  1. Jerome C Nwachukwu

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Sathish Srinivasan

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Nelson E Bruno

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Alex A Parent

    University of Illinois, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Travis S Hughes

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Julie A Pollock

    University of Illinois, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Olsi Gjyshi

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Valerie Cavett

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jason Nowak

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Ruben D Garcia-Ordonez

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. René Houtman

    PamGene International, Den Bosch, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  12. Patrick R Griffin

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Douglas J Kojetin

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. John A Katzenellenbogen

    University of Illinois, Urbana, United States
    Competing interests
    The authors declare that no competing interests exist.
  15. Michael D Conkright

    The Scripps Research Institute, Jupiter, United States
    Competing interests
    The authors declare that no competing interests exist.
  16. Kendall W Nettles

    The Scripps Research Institute, Jupiter, United States
    For correspondence
    knettles@scripps.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Leemor Joshua-Tor, Cold Spring Harbor Laboratory, United States

Publication history

  1. Received: December 12, 2013
  2. Accepted: April 5, 2014
  3. Accepted Manuscript published: April 25, 2014 (version 1)
  4. Version of Record published: May 13, 2014 (version 2)

Copyright

© 2014, Nwachukwu et al.

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jerome C Nwachukwu
  2. Sathish Srinivasan
  3. Nelson E Bruno
  4. Alex A Parent
  5. Travis S Hughes
  6. Julie A Pollock
  7. Olsi Gjyshi
  8. Valerie Cavett
  9. Jason Nowak
  10. Ruben D Garcia-Ordonez
  11. René Houtman
  12. Patrick R Griffin
  13. Douglas J Kojetin
  14. John A Katzenellenbogen
  15. Michael D Conkright
  16. Kendall W Nettles
(2014)
Resveratrol modulates the inflammatory response via an estrogen receptor-signal integration network
eLife 3:e02057.
https://doi.org/10.7554/eLife.02057

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