Rel A/p65 is required for cytokine-induced myotube atrophy.
Rel A/p65 is required for cytokine-induced myotube atrophy.
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DOI：
10.1152/ajpcell.00111.2012
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发表时间：
2012-07
期刊：
影响因子：
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通讯作者：
Takuo Yamaki;Chia-Ling Wu;Michael Gustin;Jamie K. Lim;R. Jackman;S. Kandarian
中科院分区：
文献类型：
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作者：
Takuo Yamaki;Chia-Ling Wu;Michael Gustin;Jamie K. Lim;R. Jackman;S. Kandarian
肌肉萎缩可由与促炎/分解代谢细胞因子升高相关的全身性疾病引发，而这反过来又被认为是肌肉萎缩的原因。本研究发现，在C2C12和L6肌管中，外源性TNF-α、IL-1α、IL-1β和TNF相关的凋亡弱诱导剂的作用下，NF-κB的活化需要典型的NF-κB转录因子Rel A (p65)，而不是IL-6。所有5种细胞因子均可诱导C2C12肌管萎缩，抑制p65可逆转萎缩，这是由于TNF-α、IL-1α、IL-1β、TNF相关的细胞凋亡弱诱导剂，而非IL-6的作用。p65也是TNF-α-诱导的萎缩和炎症基因表达增加所必需的。TNF-α-和il -1β-处理的肌管增加了IL-6蛋白的表达，但使用IL-6阻断抗体显示IL-6的产生不会导致萎缩。这些数据表明p65是一种必需的转录因子，介导培养肌管中四种不同细胞因子的分解代谢作用，但IL-6通过不同的机制起作用。
Muscle atrophy can be triggered by systemic illnesses that are associated with elevated proinflammatory/catabolic cytokines, which, in turn, are thought to contribute to muscle wasting. In this study, we found that the prototypical NF-κB transcription factor, Rel A (p65), is required for NF-κB activation in C2C12 and L6 myotubes due to treatment with exogenous TNF-α, IL-1α, IL-1β, TNF-related weak inducer of apoptosis, but not IL-6. All five cytokines induced atrophy in C2C12 myotubes, and inhibition of p65 reversed atrophy due to TNF-α, IL-1α, IL-1β, TNF-related weak inducer of apoptosis, but not IL-6 treatment. p65 was also required for TNF-α-induced increase in atrophy and inflammatory gene expression. TNF-α- and IL-1β-treated myotubes increased IL-6 protein expression, but use of an IL-6 blocking antibody showed that the IL-6 production did not contribute to atrophy. These data show that p65 is a required transcription factor mediating the catabolic effects of four different cytokines in cultured myotubes, but IL-6 works by a different mechanism.