Genetic deletion of mPGES-1 abolishes PGE2 production in murine dendritic cells and alters the cytokine profile, but does not affect maturation or migration

We undertook this study to determine the role of Microsomal PGE Synthase-1 (mPGES-1), and mPGES-1-generated Prostaglandin (PG) E-2 on Dendritic Cell (DC) phenotype and function. Using mPGES-1 Knock-Out (KO) mice, we generated bone marrow derived DCs and determined their eicosanoid production profile, cell surface marker expression, and cytokine production. We also assessed DC migratory and functional capacity in vivo. Compared to wild-type, mPGES-1 deficient DCs exhibited a markedly attenuated increase in PGE(2) production upon LPS stimulation, and displayed preferential shunting towards PGD(2) production. mPGES-1 KO DCs did not display deficiencies in maturation, migration or ability to sensitize T cells. However, mPGES-1 deficient DCs generated reduced amounts of the Th1 cytokine IL-12, which may in part be due to increased PGD(2) rather than decreased PGE(2). These findings provide useful information on the effects of inducible PGE(2) on the innate immune system, and have important implications regarding potential consequences of pharmacologic mPGES-1 inhibition. (C) 2010 Elsevier Ltd. All rights reserved.