Fatty acid-mediated inhibition of IL-12 production by murine macrophages is independent of PPAR(gamma)

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: PPAR(alpha), PPAR(delta)/(beta) and PPAR(gamma). PPAR(gamma) is expressed in immune cells, such as T cells and macrophages. Two PPAR(gamma) 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 PPAR(gamma). 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 PPAR(gamma) 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 PPAR(gamma).