Prostaglandin E2 stimulates COX-2 expression via mitogen-activated protein kinase p38 but not ERK in human follicular dendritic cell-like cells

Abstract

BackgroundProstaglandin E2 (PGE2) is an endogenous lipid mediator of inflammation. Its production is regulated by the rate-limiting upstream enzyme cyclooxygenase-2 (COX-2). We have recently demonstrated that the major cell type expressing COX-2 in the germinal center is follicular dendritic cell (FDC). In this study, to elucidate the molecular mechanism of PGE2 in COX-2 production, we asked whether mitogen-activated protein kinases ERK and p38 might regulate COX-2 expression.ResultsFDC-like cells were used to analyze the phosphorylation kinetics of ERK and p38 and the impact of genetic knockdown. PGE2 stimulation gave rise to a rapid increase of p38 but not ERK phosphorylation. In contrast, IL-1β induced phosphorylation of both MAPKs. Knockdown of p38 resulted in a marked suppression of COX-2 expression induced by either PGE2 or IL-1β. ERK knockdown did not significantly affect the effect of PGE2 and IL-1β on COX-2 induction. The differential results of p38 and ERK siRNA transfection were reproduced in the production of prostaglandins and in experiments performed with pharmacologic inhibitors.ConclusionsOur data indicate that p38 is essentially required for PGE2 to induce COX-2 expression in FDC-like cells. The current study helps to expand our understanding of the biological function of FDC at the molecular level and provides a potential rationale for the pharmacologic or genetic approaches to regulate p38 MAPK in the treatment of various inflammatory disorders.