Paradoxical stimulation of cyclooxygenase-2 expression by glucocorticoids via a cyclic AMP response element in human amnion fibroblasts.

ABSTRACT: Human amnion fibroblasts produce abundant prostaglandins toward the end of gestation, which is one of the major events leading to parturition. In marked contrast to its well-described antiinflammatory effect, glucocorticoids have been shown to up-regulate cyclooxygenase-2 (COX-2) expression in human amnion fibroblasts. The mechanisms underlying this paradoxical induction of COX-2 by glucocorticoids have not been resolved. Using cultured human amnion fibroblasts, we found that the induction of COX-2 mRNA expression by cortisol was a glucocorticoid receptor (GR)-dependent process requiring ongoing transcription. Upon transfection of a COX-2 promoter-driven reporter gene into the amnion fibroblasts, cortisol stimulated the COX-2 promoter activity. This was abolished by mutagenesis of a cAMP r

SUBMITTER: Zhu XO 

PROVIDER: S-EPMC5419155 | biostudies-literature | 2009 Nov

REPOSITORIES: biostudies-literature