Journal article
Oxidative metabolism and PGC-1beta attenuate macrophage-mediated inflammation.
- 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.
- Publication status:
- Published
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- Publisher copy:
- 10.1016/j.cmet.2006.05.011
Authors
- Journal:
- Cell metabolism More from this journal
- Volume:
- 4
- Issue:
- 1
- Pages:
- 13-24
- Publication date:
- 2006-07-01
- DOI:
- EISSN:
-
1932-7420
- ISSN:
-
1550-4131
- Language:
-
English
- Keywords:
-
- Pubs id:
-
pubs:18084
- UUID:
-
uuid:32dadd9c-617b-49ce-906a-310ecce44d31
- Local pid:
-
pubs:18084
- Source identifiers:
-
18084
- Deposit date:
-
2012-12-19
- ARK identifier:
Terms of use
- Copyright date:
- 2006
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