15-Deoxy-delta(12,14)-prostaglandin J(2) inhibits IL-10 and IL-12 production by macrophages.
15-Deoxy-Delta(12,14)-prostaglandin J(2) (dPGJ(2)) is a metabolite of prostaglandin D(2), that binds to peroxisome proliferator-activated receptor gamma (PPARgamma). PPARgamma and prostaglandin D(2) synthase, which is required for dPGJ(2) synthesis, are predominantly expressed in macrophages. In contrast, IL-10 and IL-12 produced by macrophages stimulate Th1 and Th2 immune response, respectively. This study investigated the effect of dPGJ(2) on IL-10 and IL-12 production by macrophages in response to lipopolysaccharide (LPS). Our data clearly demonstrated that dPGJ(2) inhibits LPS-induced IL-10 and IL-12 production by macrophages. A different agonist of PPARgamma, 13-hydroxyoctadecadienoic acid, similarly inhibited the production of IL-10 and IL-12 in response to LPS. Further, dPGJ(2) did not appear to act through the PGD(2) receptor. These results suggest that dPGJ(2) may inhibit LPS-induced IL-10 and IL-12 production by macrophages through PPARgamma.
Azuma
Y
Y
Department of Pharmacology, Osaka Dental University, 8-1 Kuzuhahanazono-cho, Osaka, Hirakata, 573-1121, Japan. aazuma@cc.osaka-dent.ac.jp
Shinohara
M
M
Wang
P L
PL
Ohura
K
K
D000818:Animals; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D008041:Linoleic Acids / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000378:metabolism; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000819:agonists / Q000378:metabolism
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D008041:Linoleic Acids; D008070:Lipopolysaccharides; D018160:Receptors, Cytoplasmic and Nuclear; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D014157:Transcription Factors; D016753:Interleukin-10; D018664:Interleukin-12; C024348:13-hydroxy-9,11-octadecadienoic acid; D015230:Prostaglandin D2; C036293:prostaglandin D2 receptor