期刊
CELL METABOLISM
卷 4, 期 1, 页码 13-24出版社
CELL PRESS
DOI: 10.1016/j.cmet.2006.05.011
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资金
- NCI NIH HHS [P30 CA021765, P30 CA 21765] Funding Source: Medline
- NHLBI NIH HHS [R01 HL076746, HL076746] Funding Source: Medline
- NIAID NIH HHS [AI062921, T32 AI007290, R01 AI062921] Funding Source: Medline
- NIDDK NIH HHS [K08 DK062386, DK062386] Funding Source: Medline
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 PPAR gamma-coactivator-1 beta (PGC-1 beta) induce macrophage programs for fatty acid oxidation and mitochondrial biogenesis. Transgenic expression of PGC-1 beta primes macrophages for alternative activation and strongly inhibits proinflammatory cytokine production, whereas inhibition of oxidative metabolism or RNAi-mediated knockdown of PGC-1 beta attenuates this immune response. These data elucidate a molecular pathway that directly links mitochondrial oxidative metabolism to the antiinflammatory program of macrophage activation, suggesting a potential role for metabolic therapies in treating atherogenic inflammation.
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