Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

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.

Original publication

DOI

10.1016/j.cmet.2006.05.011

Type

Journal article

Journal

Cell Metab

Publication Date

07/2006

Volume

4

Pages

13 - 24

Keywords

Animals, Cells, Cultured, Energy Metabolism, Fatty Acids, Feedback, Physiological, Glucose, Inflammation, Interferon-gamma, Interleukin-4, Lipopolysaccharides, Macrophage Activation, Macrophages, Mice, Mice, Transgenic, Mitochondria, Models, Biological, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, STAT6 Transcription Factor, Trans-Activators, Transcription Factors