|Budget Amount *help
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2002: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
15-Deoxy-Δ^<12,14>-prostaglandin J_2 (dPGJ_2) is a metabolite of prostaglandin D_2, that binds to peroxisome proliferator-activated receptor γ (PPARγ). PPARγ 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 PPARγ, *3-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 PPARγ. Prostaglandin D_2 (PGD_2) acts via the adenyl cyclase-coupled receptor for PGD_2 (DP receptor). Here we present evidence that BW245C, a DP receptor agonist, modulates macrophage functions related to natural immunity. BW245C inhibited macrophage chemotaxis at concentrations of 0.1 to 10 μM and phagocytosis of Escherichia coli by macrophages at a concentration of 10 μM. In addition, BW245C inhibited the production of superoxide anion by PMA-stimulated macrophages at concentrations of 0.1 to 10 μM and nitrite production by LPS-stimulated macrophages at a concentration of 10 μM. In contrast, BW245C potentiated the production of TNF-α, a pro-inflammatory cytokine, by LPS-stimulated macrophages at concentrations of 1 to 10 μM. These results suggest that PGD_2 may modulate macrophage functions related to natural immunity via DP receptor.