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

Abstract

Background: Prostaglandin 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. Results: FDC-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. Conclusions: Our 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.