IL-6-induced skeletal muscle atrophy
IL-6-induced skeletal muscle atrophy
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DOI：
10.1152/japplphysiol.01026.2004
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发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Adams, GR
中科院分区：
文献类型：
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作者：
Haddad, F;Zaldivar, F;Adams, GR
在疾病状态和许多外表健康的老年人中，循环白细胞介素6的慢性、低水平升高是可以观察到的。在高强度、长时间的运动后，血浆IL-6水平也会升高。在骨骼肌的背景下，IL-6被不同的报道调节碳水化合物和脂肪代谢，增加卫星细胞的增殖，或导致肌肉萎缩。在目前的研究中，我们使用了一种啮齿动物局部输注模型，将适度水平的IL-6直接输送到体内的单个靶肌肉中，与运动后或患有慢性低水平炎症的老年人的水平相当。这项研究的目的是研究IL-6对骨骼肌的直接影响，在这种细胞因子没有系统性变化的情况下。数据包括细胞因子和生长因子信号(磷酸化和mRNA含量)的细胞和分子标记，以及检测肌肉萎缩的测量。IL-6注射导致以肌原纤维蛋白优先丢失(-17%)为特征的肌肉萎缩。IL-6使核糖体S6激酶(-60%)和STAT5(-33%)的磷酸化水平降低，而STAT3的磷酸化水平增加近一倍。在注入IL-6的肌肉中看到的变化表明，与生长因子相关的信号平衡发生了变化，有利于更多的分解代谢。这提示，生长因子介导的细胞内信号转导下调可能是IL-6升高导致肌肉萎缩的机制之一。
Chronic, low-level elevation of circulating interleukin (IL)-6 is observed in disease states as well as in many outwardly healthy elderly individuals. Increased plasma IL-6 is also observed after intense, prolonged exercise. In the context of skeletal muscle, IL-6 has variously been reported to regulate carbohydrate and lipid metabolism, increase satellite cell proliferation, or cause muscle wasting. In the present study, we used a rodent local infusion model to deliver modest levels of IL-6, comparable to that present after exercise or with chronic low-level inflammation in the elderly, directly into a single target muscle in vivo. The aim of this study was to examine the direct effects of IL-6 on skeletal muscle in the absence of systemic changes in this cytokine. Data included cellular and molecular markers of cytokine and growth factor signaling ( phosphorylation and mRNA content) as well as measurements to detect muscle atrophy. IL-6 infusion resulted in muscle atrophy characterized by a preferential loss of myofibrillar protein ( -17%). IL-6 induced a decrease in the phosphorylation of ribosomal S6 kinase ( - 60%) and STAT5 ( - 33%), whereas that of STAT3 was increased approximately twofold. The changes seen in the IL-6-infused muscles suggest alterations in the balance of growth factor-related signaling in favor of a more catabolic profile. This suggests that downregulation of growth factor-mediated intracellular signaling may be a mechanism contributing to the development of muscle atrophy induced by elevated IL-6.