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Oxidative metabolism and PGC-1β attenuate macrophage-mediated inflammation
- Source :
- Cell Metabolism. 4:13-24
- Publication Year :
- 2006
- Publisher :
- Elsevier BV, 2006.
-
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.
- Subjects :
- Lipopolysaccharides
Physiology
HUMDISEASE
Mice, Transgenic
Inflammation
Biology
Models, Biological
Article
Proinflammatory cytokine
Interferon-gamma
Mice
03 medical and health sciences
0302 clinical medicine
medicine
Animals
Macrophage
Molecular Biology
Macrophage inflammatory protein
Cells, Cultured
Interleukin 4
030304 developmental biology
STAT6
Feedback, Physiological
0303 health sciences
Macrophages
Fatty Acids
Cell Biology
Macrophage Activation
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
Mitochondria
3. Good health
Cell biology
Glucose
Mitochondrial biogenesis
SIGNALING
030220 oncology & carcinogenesis
Trans-Activators
STAT protein
Interleukin-4
medicine.symptom
Energy Metabolism
STAT6 Transcription Factor
Transcription Factors
Subjects
Details
- ISSN :
- 15504131
- Volume :
- 4
- Database :
- OpenAIRE
- Journal :
- Cell Metabolism
- Accession number :
- edsair.doi.dedup.....e57513c8778441eb44b2d793d88965b8