Cross talk between glucocorticoid and estrogen receptors occurs at a subset of proinflammatory genes

Aleksandra Cvoro, Chaoshen Yuan, Sreenivasan Paruthiyil, Oliver H. Miller, Keith R. Yamamoto, Dale C. Leitman

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

Glucocorticoids exert potent anti-inflammatory effects by repressing proinflammatory genes. We previously demonstrated that estrogens repress numerous proinflammatory genes in U2OS cells. The objective of this study was to determine if cross talk occurs between the glucocorticoid receptor (GR) and estrogen receptor (ER)a. The effects of dexamethasone (Dex) and estradiol on 23 proinflammatory genes were examined in human U2OS cells stably transfected with ERa or GR. Three classes of genes were regulated by ERa and/or GR. Thirteen genes were repressed by both estradiol and Dex (ER/GR-repressed genes). Five genes were repressed by ER (ER-only repressed genes), and another five genes were repressed by GR (GR-only repressed genes). To examine if cross talk occurs between ER and GR at ER/GR-repressed genes, U2OS-GR cells were infected with an adenovirus that expresses ERa. The ER antagonist, ICI 182780 (ICI), blocked Dex repression of ER/GR-repressed genes. ICI did not have any effect on the GR-only repressed genes or genes activated by Dex. These results demonstrate that ICI acts on subset of proinflammatory genes in the presence of ERa but not on GR-activated genes. ICI recruited ERa to the IL-8 promoter but did not prevent Dex recruitment of GR. ICI antagonized Dex repression of the TNF response element by blocking the recruitment of nuclear coactivator 2. These findings indicate that the ICI-ERa complex blocks Dex-mediated repression by interfering with nuclear coactivator 2 recruitment to GR. Our results suggest that it might be possible to exploit ER and GR cross talk for glucocorticoid therapies using drugs that interact with ERs.

Original languageEnglish (US)
Pages (from-to)4354-4360
Number of pages7
JournalJournal of Immunology
Volume186
Issue number7
DOIs
StatePublished - Apr 1 2011

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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