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 t o be important in the induction of PGHS-2 gene expression. This was demonst rated by showing that coexpression of CREB stimulated native but not CRE mu tant promoter and that IL-1 beta and PMA induced less activity with the mut ant promoter as compared to the native promoter. The effect of dexamethason e on IL-1 beta and PMA induced promoter activities was further examined. IL -1 beta or PMA induced activity was blocked by dexamethasone, whereas IL-1 beta or PMA induced mutant activity was not responsive to dexamethasone. Di rect 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-1 beta and PMA as well as the su ppression of expression by dexamethasone in amnion-derived cells.