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 synthes ized in the amnion and that this synthesis increases during labor. The purp ose of this study was to clarify the mechanism for the expression of cycloo xygenase-2 (COX-2) mRNA and the PGE(2) synthesis of amnion-derived (WISH) c ells. Study design: Cells were cultured and treated by 12-O-tetradecanoylph orbol-13-acetate (TPA) and dexamethasone (DEX). PGE(2) in the culture mediu m 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 2 h, but this production appeared to continue after 4 h of incubation. PGE(2) pr oduction was significantly increased by TPA and suppressed by treatment wit h 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 1.5 h. The st rongest expression of COX-2 mRNA was observed at 2 h incubation. After pre- treatment with TPA for 1 h, the TPA-induced COX-2 mRNA was suppressed by tr eatment with DEX for I or 2 h incubation in a dose-dependent manner. Conclu sions: These results suggest that COX-2 mRNA is induced by TPA which activa te protein kinase C, and suppressed by DEX in WISH cells. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.