Prostaglandin E2 synthesis in human monocyte-derived dendritic cells

Prostaglandin E-2 (PGE(2)), which is generated by the enzymatic activity of cyclooxygenase-1 and -2 (COX-1/2), plays a central role in the maturation process of dendritic cells (DC). Since regulation of COX-1/2 expression in human DC is only partially understood, we addressed the expression and activity of COX-1/2 in these cells. Here we show that lipopolysaccharide (lps) induces COX-2 mRNA and protein synthesis as well as the release of PGE(2) in human interieukin-4 and granulocyte/macrophage colony-stimulating factor-differentiated monocyte-derived DC cultivated in the presence of 1% human plasma. Moreover, we found that lps induces p38 stress-activated protein kinase (p38) in these cells and inhibitors of p38 blocked lps induced COX-2 expression and activity. Our data indicate that during lps-induced maturation p38 regulates COX-2 expression and PGE(2) synthesis in DC.