期刊
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
卷 297, 期 1, 页码 E174-E183出版社
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpendo.90632.2008
关键词
peroxisome proliferator-activated receptor-gamma; nuclear factor-kappa B; rosiglitazone; inflammation; type 2 diabetes mellitus; skeletal muscle atrophy
资金
- European Union [QLK6-CT-2002-02285]
- Royal Netherlands Academy of Arts and Sciences
- VENI [916.56.112]
Remels AH, Langen RC, Gosker HR, Russell AP, Spaapen F, Voncken JW, Schrauwen P, Schols AM. PPAR gamma inhibits NF-kappa B-dependent transcriptional activation in skeletal muscle. Am J Physiol Endocrinol Metab 297: E174-E183, 2009. First published May 5, 2009; doi: 10.1152/ajpendo.90632.2008.-Skeletal muscle pathology associated with a chronic inflammatory disease state ( e. g., skeletal muscle atrophy and insulin resistance) is a potential consequence of chronic activation of NF-kappa B. It has been demonstrated that peroxisome proliferator-activated receptors (PPARs) can exert anti-inflammatory effects by interfering with transcriptional regulation of inflammatory responses. The goal of the present study, therefore, was to evaluate whether PPAR activation affects cytokine-induced NF-kappa B activity in skeletal muscle. Using C2C12 myotubes as an in vitro model of myofibers, we demonstrate that PPAR, and specifically PPAR gamma, activation potently inhibits inflammatory mediator-induced NF-kappa B transcriptional activity in a time- and dose-dependent manner. Furthermore, PPAR gamma activation by rosiglitazone strongly suppresses cytokine-induced transcript levels of the NF-kappa B-dependent genes intracellular adhesion molecule 1 (ICAM-1) and CXCL1 ( KC), the murine homolog of IL-8, in myotubes. To verify whether muscular NF-kappa B activity in human subjects is suppressed by PPAR gamma activation, we examined the effect of 8 wk of rosiglitazone treatment on muscular gene expression of ICAM-1 and IL-8 in type 2 diabetes mellitus patients. In these subjects, we observed a trend toward decreased basal expression of ICAM-1 mRNA levels. Subsequent analyses in cultured myotubes revealed that the anti-inflammatory effect of PPAR gamma activation is not due to decreased RelA translocation to the nucleus or reduced RelA DNA binding. These findings demonstrate that muscle-specific inhibition of NF-kappa B activation may be an interesting therapeutic avenue for treatment of several inflammation-associated skeletal muscle abnormalities.
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