Differential Expression and Regulation of Microsomal Prostaglandin E2 Synthase in Human Fetal Membranes and Placenta with Infection and in Cultured Trophoblast Cells

Abstract

We have evaluated the effect of chorioamnionitis on the protein expression of microsomal and cytosolic prostaglandin E(2) synthases (mPGES and cPGES) in preterm human placentae (PL) and fetal membranes (FM), by Western blot and immunohistochemistry, as well as the regulatory effect of IL-1beta and TNF-alpha on mPGES, cPGES, and cyclooxygenase (COX)-2 expression in villous trophoblast (VT) and chorion trophoblast (CT) cell cultures. mPGES localized to the syncytiotrophoblast and vascular endothelium in PL and to the amnion epithelium, CT, and decidual cells in FM. cPGES protein was localized only to the syncytiotrophoblast in PL and had the same profile of expression as mPGES in FM. With infection, there was an increase in mPGES expression in PL and a decrease in the expression in FM. cPGES protein did not change in either PL or FM with infection. In VT cells in culture, IL-1beta up-regulated COX-2 protein expression but did not affect mPGES. However, TNF-alpha increased both mPGES and COX-2 protein expression in these cells. In CT cells in culture, IL-1beta and TNF-alpha increased both mPGES and COX-2 protein levels. Neither IL-1beta nor TNF-alpha affected cPGES in either VT or CT cells. We conclude that protein levels of mPGES, as well as COX-2, can be stimulated by cytokines, potentially contributing to the increased prostaglandin production at the time of infection-driven preterm labor. However, multiple mechanisms, which apparently are inductor- and cell-type-specific, exist for the regulation of these enzymes.