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Cell Metab. 2006 Jul;4(1):13-24.

Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation.

Author information

  • 1Division of Endocrinology, Metabolism and Gerontology, Department of Medicine and Graduate Program in Immunology, Stanford University School of Medicine, Stanford, California 94305, USA.

Erratum in

  • Cell Metab. 2006 Sep;4(3):255. Wagner, Roger A [added].

Abstract

Complex interplay between T helper (Th) cells and macrophages contributes to the formation and progression of atherosclerotic plaques. While Th1 cytokines promote inflammatory activation of lesion macrophages, Th2 cytokines attenuate macrophage-mediated inflammation and enhance their repair functions. In spite of its biologic importance, the biochemical and molecular basis of how Th2 cytokines promote maturation of anti-inflammatory macrophages is not understood. We show here that in response to interleukin-4 (IL-4), signal transducer and activator of transcription 6 (STAT6) and PPARgamma-coactivator-1beta (PGC-1beta) induce macrophage programs for fatty acid oxidation and mitochondrial biogenesis. Transgenic expression of PGC-1beta primes macrophages for alternative activation and strongly inhibits proinflammatory cytokine production, whereas inhibition of oxidative metabolism or RNAi-mediated knockdown of PGC-1beta attenuates this immune response. These data elucidate a molecular pathway that directly links mitochondrial oxidative metabolism to the anti-inflammatory program of macrophage activation, suggesting a potential role for metabolic therapies in treating atherogenic inflammation.

Comment in

PMID:
16814729
[PubMed - indexed for MEDLINE]
PMCID:
PMC1904486
Free PMC Article

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