15-Deoxy-Δ12,14-prostaglandin J2 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 (PPAR gamma). PPAR gamma 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 PPAR gamma, 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 PPAR gamma. (C) 2001 Academic Press.