title: Genetic deletion of mPGES-1 abolishes PGE2 production in murine dendritic cells and alters the cytokine profile, but does not affect maturation or migration.
abstract: We undertook this study to determine the role of Microsomal PGE Synthase-1 (mPGES-1), and mPGES-1-generated Prostaglandin (PG) E2 on Dendritic Cell (DC) phenotype and function. Using mPGES-1 KnockOut (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 PGE2 production upon LPS stimulation, and displayed preferential shunting towards PGD2 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 PGD2 rather than decreased PGE2. These findings provide useful information on the effects of inducible PGE2 on the innate immune system, and have important implications regarding potential consequences of pharmacologic mPGES-1 inhibition.
authors.affiliation: Department of Internal Medicine, University of Michigan, Ann Arbor, 48109, USA.
authors.forename: S U
authors.initials: SU
authors.lastname: Monrad
authors.forename: F
authors.initials: F
authors.lastname: Kojima
authors.forename: M
authors.initials: M
authors.lastname: Kapoor
authors.forename: E L
authors.initials: EL
authors.lastname: Kuan
authors.forename: S
authors.initials: S
authors.lastname: Sarkar
authors.forename: G J
authors.initials: GJ
authors.lastname: Randolph
authors.forename: L J
authors.initials: LJ
authors.lastname: Crofford
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000378:metabolism*; D015232:Dinoprostone / Q000096:biosynthesis*; D017353:Gene Deletion; D018664:Interleukin-12 / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D000071876:Prostaglandin-E Synthases; D051381:Rats
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D018664:Interleukin-12; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone