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

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.