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

Published online by Cambridge University Press:  09 March 2007

Meijuan Zhang  and
Kevin L. Fritsche
Meijuan Zhang
Affiliation:
Department of Animal Sciences and the Nutritional Sciences Graduate Program, University of Missouri-Columbia, Columbia, MO 65211, USA
Kevin L. Fritsche*
Affiliation:
Department of Animal Sciences and the Nutritional Sciences Graduate Program, University of Missouri-Columbia, Columbia, MO 65211, USA
*
*Corresponding author: Dr Kevin Fritsche, fax +1 573 882 6827, email FritscheK@missouri.edu
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Abstract

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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-Δ12,14-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 acidsPeroxisome proliferator-activated receptor-γInterleukin 12Macrophages
Type
Research Article
Information
British Journal of Nutrition , Volume 91 , Issue 5 , May 2004 , pp. 733 - 739
Copyright
Copyright © The Nutrition Society 2004

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