title: Fatty acid-mediated inhibition of IL-12 production by murine macrophages is independent of PPARgamma.
abstract: Our laboratory has reported that n-3 PUFA can reduce host resistance to Listeria infection, in part, by impairing in vivo IL-12 biosynthesis. Recently, PUFA were shown to be ligands for PPAR, a novel family of nuclear receptors with three isoforms: PPARalpha, PPARdelta/beta and PPARgamma. PPARgamma is expressed in immune cells, such as T cells and macrophages. Two PPARgamma agonists, 15-deoxy-delta(12,14)-prostaglandin (PG) J2 and rosiglitazone, have been shown to have immunomodulatory activity in vitro, including inhibiting IL-12 biosynthesis. We hypothesized that n-3 PUFA inhibit IL-12 production through activating PPARgamma. We used thioglycolate-elicited mouse peritoneal macrophages to study the effect of various fatty acids and their oxidized metabolites on in vitro IL-12 production. Our present results demonstrate that both n-3 and n-6 PUFA can reduce in vitro IL-12 biosynthesis, though less potently than 15-deoxy-PGJ2 and rosiglitazone. GW9662, a PPARgamma antagonist, reversed the inhibitory effect of rosiglitazone, but not that of PUFA. Our present findings suggest that fatty acid-mediated inhibition of IL-12 production is independent of PPARgamma.
authors.affiliation: Department of Animal Sciences and the Nutritional Sciences Graduate Program, University of Missouri-Columbia, Columbia, MO 65211, USA.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Zhang
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Fritsche
mesh_terms: D000813:Anilides / Q000276:immunology / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000276:immunology; D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000276:immunology; D005231:Fatty Acids, Unsaturated / Q000276:immunology*; D005260:Female; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000276:immunology; D008024:Ligands; D019787:Linoleic Acid / Q000276:immunology; D017737:Macrophages, Peritoneal / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000276:immunology*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000276:immunology; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C457499:2-chloro-5-nitrobenzanilide; D000813:Anilides; D005231:Fatty Acids, Unsaturated; D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D045162:Thiazolidinediones; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D018664:Interleukin-12; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D019787:Linoleic Acid