The effect of dexamethasone on expression of mitogen-induced cyclooxygenase-2 mRNA by amnion-derived (WISH) cells

Objectives : It has been reported that prostaglandin E 2 (PGE 2 ) is synthesized in the amnion and that this synthesis increases during labor. The purpose of this study was to clarify the mechanism for the expression of cyclooxygenase-2 (COX-2) mRNA and the PGE 2 synthesis of amnion-derived (WISH) cells. Study design : Cells were cultured and treated by 12- O -tetradecanoylphorbol-13-acetate (TPA) and dexamethasone (DEX). PGE 2 in the culture medium was measured by ELISA. Total RNA was extracted from the cells, and COX-2 mRNA expression was analyzed by Northern blot analysis. Results : During the time course of PGE 2 production in response to TPA stimulation, the PGE 2 production could not be detected until incubation had continued for 2h, but this production appeared to continue after 4h of incubation. PGE 2 production was significantly increased by TPA and suppressed by treatment with TPA and DEX. During the time course of COX-2 mRNA expression in response to treatment with TPA, the COX-2 mRNA band was detected after 1.5h. The strongest expression of COX-2 mRNA was observed at 2h incubation. After pre-treatment with TPA for 1h, the TPA-induced COX-2 mRNA was suppressed by treatment with DEX for 1 or 2h incubation in a dose-dependent manner. Conclusions : These results suggest that COX-2 mRNA is induced by TPA which activate protein kinase C, and suppressed by DEX in WISH cells.