Expression of tumor necrosis factor-alpha in regenerating muscle fibers in inflammatory and non-inflammatory myopathies

Abstract

The expression level of tumor necrosis factor (TNF)-alpha is elevated in idiopathic inflammatory myopathies and Duchenne muscular dystrophy (DMD), but the precise role of TNF-alpha is unknown. To elucidate the possible role of TNF-alpha, we investigated the expression of TNF-alpha and its receptor in polymyositis (PM), dermatomyositis (DM), and DMD using in situ hybridization (ISH) and immunohistochemistry. We showed that TNF-alpha mRNA and protein were present in muscle fibers. TNF-alpha-positive fibers were observed in all cases of PM, DM and DMD, but were rare or absent in neurogenic disorders and normal controls. The proportion of TNF-alpha-positive fiber showed a significant positive correlation with the proportion of regenerating fibers that were positive for the developmental form of myosin heavy chain (MHC-d). The number of TNF receptor-positive fibers was small. Some muscle fibers expressed both TNF-alpha and its receptor simultaneously. Our results indicate that TNF-alpha is produced and expressed by muscle fibers and associated with muscle regeneration.