Heat Shock Protein Families 70 and 90 in Duchenne Muscular Dystrophy and Inflammatory Myopathy: Balancing Muscle Protection and Destruction

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.