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 journalArticlepeer-review

24 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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