The Peroxisome Proliferator-activated Receptor γ Coactivator 1 α/β (PGC-1) Coactivators Repress the Transcriptional Activity of NF-κB in Skeletal Muscle Cells
The Peroxisome Proliferator-activated Receptor γ Coactivator 1 α/β (PGC-1) Coactivators Repress the Transcriptional Activity of NF-κB in Skeletal Muscle Cells
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DOI：
10.1074/jbc.m112.375253
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发表时间：
2013-01-25
影响因子：
4.8
通讯作者：
Handschin, Christoph
中科院分区：
文献类型：
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作者：
Eisele, Petra S.;Salatino, Silvia;Handschin, Christoph
持续性的低度炎症伴随着许多慢性疾病，这些疾病是由身体不活动引起的，并通过运动得到改善。运动的有益作用在很大程度上是由过氧化物酶体增殖物激活受体γ共激活因子（PGC）1 α介导的，而其损失与局部和全身炎症标志物的传播相关。我们检测了PGC-1 α和相关的PGC-1 β对用TNF α、Toll样受体激动剂和游离脂肪酸刺激肌细胞后的炎性细胞因子的影响。PGC-1通过靶向NF-κ B信号传导差异抑制促炎细胞因子的表达有趣的是，PGC-1 α和PGC-1 β均降低NF-κ B家族成员p65的磷酸化，从而降低其转录激活潜力。总之，本文提供的数据表明，PGC-1共激活因子能够抑制肌肉细胞中的炎症事件，并在代谢和免疫途径之间提供分子联系。因此，PGC-1代表了有吸引力的目标，不仅可以改善2型糖尿病等疾病的代谢健康，还可以限制这些患者的有害低度炎症。
A persistent, low-grade inflammation accompanies many chronic diseases that are promoted by physical inactivity and improved by exercise. The beneficial effects of exercise are mediated in large part by peroxisome proliferator-activated receptor gamma coactivator (PGC) 1 alpha, whereas its loss correlates with propagation of local and systemic inflammatory markers. We examined the influence of PGC-1 alpha and the related PGC-1 beta on inflammatory cytokines upon stimulation of muscle cells with TNF alpha, Toll-like receptor agonists, and free fatty acids. PGC-1s differentially repressed expression of proinflammatory cytokines by targeting NF-kappa B signaling. Interestingly, PGC-1 alpha and PGC-1 beta both reduced phoshorylation of the NF-kappa B family member p65 and thereby its transcriptional activation potential. Taken together, the data presented here show that the PGC-1 coactivators are able to constrain inflammatory events in muscle cells and provide a molecular link between metabolic and immune pathways. The PGC-1s therefore represent attractive targets to not only improve metabolic health in diseases like type 2 diabetes but also to limit the detrimental, low-grade inflammation in these patients.