Volume 91, Issue 5, May (2004), pp. 733-739 © The Author 2004
doi:10.1079/BJN20041096

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Fatty acid-mediated inhibition of IL-12 production by murine macrophages is independent of PPARγ

Meijuan Zhang¹ and Kevin L. Fritsche^1
1Department of Animal Sciences and the Nutritional Sciences Graduate Program, University of Missouri-Columbia, Columbia, MO 65211, USA

 (Received 4 August 2003–Revised 12 December 2002–Accepted 7 January 2004)

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: PPARα, PPARδ/β and PPARγ. PPARγ is expressed in immune cells, such as T cells and macrophages. Two PPARγ agonists, 15-deoxy-Δ^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 PPARγ. 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 PPARγ 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 PPARγ.

Keywords:
Polyunsaturated fatty acids, Peroxisome proliferator-activated receptor-γ, Interleukin 12, Macrophages

Abbreviations:
AA, arachidonic acid, DHA, docosahexaenoic acid, IFN, interferon, LA, linoleic acid, LPS, lipopolysaccharide, PG, prostaglandin