Corticosteroids induce COX-2 expression in cardiomyocytes: Role of glucocorticoid receptor and C/EBP-β

Haipeng Sun, Elena Sheveleva, Beibei Xu, Hiroyasu Inoue, Tim G. Bowden, Qin M. Chen

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Psychological stress increases the level of glucocorticoids in the circulating system. We found that dexamethasone administration in adult mice elevates the expression of COX-2 in the myocardium. With isolated neonatal cardiomyocytes, corticosterone (CT) at physiologically relevant doses (0.01-1 μM) induces the expression of COX-2 gene. The induction first appeared at 4 h and remained for at least 24 h with 1 μM CT treatment. This response is likely cardiomyocyte cell type specific since CT did not induce COX-2 expression in cardiac fibroblasts and glucocorticoids are known to suppress the expression of COX-2 in lymphocytes and several organs. Corticosteroids, but not estrogen or progesterone, induce COX-2 expression. The glucocorticoid receptor (GR) antagonist mifepristone (MF) prevented CT from inducing COX-2 gene, suggesting a GR-dependent induction in cardiomyocytes. COX-2 gene promoter deletion and mutation studies indicate a role of CCAAT/enhancer binding protein-β (C/EBP-β) in CT-induced COX-2 gene expression. Chromatin immunoprecipitation assays revealed that CT caused the binding of both GR and C/EBP-β to COX-2 promoter, while MF pretreatment blocked such binding. Coimmunoprecipitation experiments demonstrated that CT treatment induced the interaction of GR with C/EBP-β. Small interfering RNA against C/EBP-β prevented CT from activating COX-2 promoter or elevating COX-2 protein. Our data suggest that the interaction between GR and C/EBP-β contributes to elevated COX-2 gene transcription by CT in cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)C915-C922
JournalAmerican Journal of Physiology - Cell Physiology
Volume295
Issue number4
DOIs
StatePublished - Oct 2008

Keywords

  • Cyclooxygenase
  • Gene expression
  • Protein-protein interaction
  • Transcription

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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