A dual role for HSP90 and HSP70 in the inflammatory myopathies: from muscle fiber protection to active invasion by macrophages

Ann N Y Acad Sci. 2009 Sep:1173:463-9. doi: 10.1111/j.1749-6632.2009.04812.x.

Abstract

Chaperones assist the metamorphosis of polypeptides to fully functional proteins. The family of heat shock proteins 70 (HSP70) bind at an early stage, while the HSP90 bind to proteins near their active conformation. We studied HSP90 and HSP70 in muscle biopsies from controls and patients diagnosed with the three main idiopathic inflammatory myopathies (IIM), namely dermatomyositis (DM), sporadic inclusion body myositis (IBM), and polymyositis (PM). Human skeletal muscle displayed constitutive levels of protein, but in IIM both HSP90 and HSP70 were upregulated. Regenerating muscle fibers of IIM and muscular dystrophy patients showed increased expression of HSP90 and HSP70, as did atrophic perifascicular muscle fibers of DM and vacuolated fibers of IBM. The infiltrates of IIM displayed weak homogeneous HSP70 staining. HSP90 were specifically upregulated in the CD68(+) cells, actively invading non-necrotic muscle fibers of IBM/PM and co-localized with inducible NO synthase. HSP90:HSP70 ratios were increased in IBM and PM tissues displaying high inflammation grade. Our results point to a multifaceted role for chaperones in muscle tissue: a general protective role for both HSP90 and HSP70 families in damaged muscle fibers, and a specific cytotoxic role for HSP90 in muscle fiber invasion typically associated with IBM and PM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Antigens, Differentiation, Myelomonocytic / metabolism
  • Biopsy
  • Blotting, Western
  • Dermatomyositis / metabolism
  • Dermatomyositis / pathology
  • HSP70 Heat-Shock Proteins / metabolism*
  • HSP70 Heat-Shock Proteins / physiology
  • HSP90 Heat-Shock Proteins / metabolism*
  • HSP90 Heat-Shock Proteins / physiology
  • Humans
  • Immunohistochemistry
  • Macrophages / metabolism
  • Macrophages / pathology
  • Muscle Fibers, Skeletal / metabolism*
  • Muscle Fibers, Skeletal / pathology
  • Myositis / metabolism*
  • Myositis / pathology
  • Myositis, Inclusion Body / metabolism
  • Myositis, Inclusion Body / pathology
  • Nitric Oxide Synthase Type II / metabolism
  • Polymyositis / metabolism
  • Polymyositis / pathology

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • CD68 antigen, human
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • Nitric Oxide Synthase Type II