Cyclic AMP response element mediates dexamethasone induced suppression of prostaglandin H synthase-2 gene expression in human amnion derived WISH cells.
A human PGHS-2 promoter fragment (300 BP) linked to the luciferase reporter was used to study the regulation of PGHS-2 gene expression in human amnion-derived WISH cells. A cyclic AMP (cAMP) response element (CRE) was found to be important in the induction of PGHS-2 gene expression. This was demonstrated by showing that coexpression of CREB stimulated native but not CRE mutant promoter and that IL-1beta and PMA induced less activity with the mutant promoter as compared to the native promoter. The effect of dexamethasone on IL-1beta and PMA induced promoter activities was further examined. IL-1beta or PMA induced activity was blocked by dexamethasone, whereas IL-1beta or PMA induced mutant activity was not responsive to dexamethasone. Direct activation of CRE by a cAMP elevating agent, isoproterenol, was found to be inhibited significantly dexamethasone. These results suggest that CRE may mediate the induction of PGHS-2 by IL-1beta and PMA as well as the suppression of expression by dexamethasone in amnion-derived cells.
Division of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, University of Kentucky, Lexington 40536-0082, USA.
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D000650:Amnion / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000235:genetics*; D051546:Cyclooxygenase 2; D004268:DNA-Binding Proteins / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D015536:Down-Regulation; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics*; D007545:Isoproterenol / Q000494:pharmacology; D008565:Membrane Proteins; D016297:Mutagenesis, Site-Directed; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics; D014162:Transfection
D004268:DNA-Binding Proteins; D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D014157:Transcription Factors; D003907:Dexamethasone; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate