Immunolocalization of tumor necrosis factor-alpha and its receptors in inflammatory myopathies

Neuromuscul Disord. 1999 Jun;9(4):239-46. doi: 10.1016/s0960-8966(98)00126-6.


Adhesion molecule upregulation occurs in inflammatory myopathies, and is one of the myriad functions of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha acts via two different receptors of 55 (TNF-R55) and 75 kD (TNF-R75). We immunolocalized TNF-alpha and its receptors in polymyositis, inclusion body myositis and dermatomyositis. In each myopathy, TNF-alpha was detected in macrophages, in myonuclei in regenerating muscle fibers, and freely dispersed in endomysial or perimysial connective tissue. Many endothelial cells in dermatomyositis expressed TNF-alpha. TNF-R55 was strongly expressed on myonuclei of regenerating muscle fibers. TNF-R75 was increased on endothelial cells in the midst of inflammatory infiltrates in each myopathy, and on perifascicular and perimysial endothelia, remote from inflammatory foci in dermatomyositis. Possible TNF-alpha-mediated effects include: increased transendothelial cell trafficking, activation of T/B cells and macrophages, induction of MHC-I gene products, and focal muscle fiber atrophy. In dermatomyositis, the upregulated TNF-R75, via its consensus elements for transcription factors, may be involved in endothelial cell degeneration. Strong TNF-R55 expression on regenerating myonuclei is consistent with a role of TNF-alpha and TNF-R55 in muscle regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Dermatomyositis / metabolism
  • Dermatomyositis / pathology
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / pathology
  • Humans
  • Immunohistochemistry
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Myositis / metabolism*
  • Myositis / pathology
  • Myositis, Inclusion Body / metabolism
  • Myositis, Inclusion Body / pathology
  • Polymyositis / metabolism
  • Polymyositis / pathology
  • Receptors, Tumor Necrosis Factor / biosynthesis
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha / metabolism*
  • Up-Regulation / physiology


  • Antigens, CD
  • Receptors, Tumor Necrosis Factor
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha