Dual effects of caspase-1, interleukin-1 beta, tumour necrosis factor-alpha and nerve growth factor receptor in inflammatory myopathies

Clin Exp Rheumatol. Jan-Feb 2003;21(1):41-8.

Abstract

Objective: To analyse the expression of factors potentially involved in skeletal muscle degeneration and regeneration in dermatomyositis (DM), systemic sclerosis (SSc), polymyositis (PM), systemic lupus erythematosus (SLE) and non-inflammatory myopathies.

Methods: Immunohistochemical staining of skeletal muscle biopsies (10 DM, 10 SSc, 10 PM, 10 SLE, 10 non-inflammatory myopathies) for tumour necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), activated caspase-1, pan-macrophage marker CD68, inducible nitric oxide synthase (NOS2) and nerve growth factor receptor (NGFR). TechMate staining robot and biotin-streptavidin protocol were used.

Results: Expression of TNF-alpha, IL-1 beta, caspase-1 and NOS2 was found in the cytoplasm and sarcolemma of dystrophic skeletal muscle fibres. TNF-alpha and IL-1 beta immunoreactive profiles were faint and few and close to satellite nuclei-containing regenerating muscle fibres both in inflammatory and non-inflammatory myopathies. NGFR expression was found in comparable areas. In non-inflammatory inherited myopathies more nuclei were caspase-1 immunoreactive whereas caspase-1 expression was rarely seen in inflammatory myopathies, implying regeneration of the affected muscle fibres.

Conclusion: Prominent expression of the proinflammatory factors TNF-alpha, IL-1 beta and NOS2 and caspase-1 is associated with muscle fibre damage, albeit when expressed to a low degree these factors may, like NGFR, contribute to muscle regeneration and healing.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Biomarkers / analysis
  • Caspase 1 / metabolism*
  • Dermatomyositis / etiology
  • Dermatomyositis / metabolism*
  • Dermatomyositis / pathology
  • Female
  • Humans
  • Immunohistochemistry
  • Interleukin-1 / metabolism*
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / metabolism
  • Lupus Erythematosus, Systemic / pathology
  • Male
  • Middle Aged
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology
  • Polymyositis / etiology
  • Polymyositis / metabolism*
  • Polymyositis / pathology
  • Receptor, Nerve Growth Factor / metabolism*
  • Regeneration / physiology
  • Scleroderma, Systemic / complications
  • Scleroderma, Systemic / metabolism
  • Scleroderma, Systemic / pathology
  • Tumor Necrosis Factor-alpha / metabolism*

Substances

  • Biomarkers
  • Interleukin-1
  • Receptor, Nerve Growth Factor
  • Tumor Necrosis Factor-alpha
  • Caspase 1