Department of Neurology and Neuromuscular Reference Center, Ghent University Hospital, Belgium.
Neuromuscul Disord. 2012 Jan;22(1):26-33. doi: 10.1016/j.nmd.2011.07.007. Epub 2011 Aug 19.
Heat shock proteins are important factors in skeletal muscle physiology and stress response. We examined the effects of chronic inflammation on the distribution of heat shock protein families 70 and 90 using immunofluorescence and Western blotting, in muscle biopsies from 33 idiopathic inflammatory myopathy patients [aged 26-66 (dermatomyositis), 17-78 (polymyositis) and 57-80 (sporadic inclusion body myositis) years], and seven Duchenne muscular dystrophy patients (aged 3-19 years). Our results reveal the multifaceted role played by chaperones in inflammatory muscle tissue. On the one hand, regenerating, atrophic and vacuolated muscle fibers displayed upregulation of both protein families. Higher levels of chaperones in challenged fibers point to the myocyte's attempt to restore and regenerate. On the other hand, heat shock proteins of the 90 family were strongly upregulated in macrophages and cytotoxic T-cells actively invading nonnecrotic muscle fibers of sporadic inclusion body myositis and polymyositis, probably conferring enhanced myocytotoxic capacity. Our data provide positive arguments for exploring heat shock protein 90-based therapy in inflammatory muscle disease.
热休克蛋白是骨骼肌生理学和应激反应的重要因素。我们通过免疫荧光和 Western blot 分析，研究了慢性炎症对 33 名特发性炎性肌病患者（年龄 26-66 岁[皮肌炎]、17-78 岁[多发性肌炎]和 57-80 岁[散发性包涵体肌炎]）和 7 名杜氏肌营养不良症患者（年龄 3-19 岁）肌肉活检中热休克蛋白家族 70 和 90 的分布的影响。我们的结果揭示了伴侣蛋白在炎性肌肉组织中发挥的多方面作用。一方面，再生、萎缩和空泡化的肌纤维上调了这两个蛋白家族。挑战纤维中伴侣蛋白水平的升高表明肌细胞试图恢复和再生。另一方面，在散发性包涵体肌炎和多发性肌炎中，巨噬细胞和细胞毒性 T 细胞积极浸润非坏死性肌纤维中 90 家族的热休克蛋白强烈上调，可能赋予了增强的肌细胞毒性能力。我们的数据为探索基于热休克蛋白 90 的治疗炎性肌肉疾病提供了积极的论据。
