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Corticosteroids induce COX-2 expression in cardiomyocytes: role of glucocorticoid receptor and CIEBP-β.
- Source :
-
American Journal of Physiology: Cell Physiology . Oct2008, Vol. 295 Issue 4, pC915-C922. 8p. 12 Graphs. - Publication Year :
- 2008
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03636143
- Volume :
- 295
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- American Journal of Physiology: Cell Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 34878488
- Full Text :
- https://doi.org/10.1152/ajpcell.90646.2007