Expression of matrix metalloproteinases in the muscle of patients with inflammatory myopathies

Young Chul Choi, Marinos C. Dalakas

Research output: Contribution to journalArticle

117 Citations (Scopus)

Abstract

Objective: To investigate the role of matrix metalloproteinases (MMPs) in the pathogenesis of inflammatory myopathies and the amyloid formation in sporadic inclusion body myositis (s-IBM). Background: MMPs comprise a family of calcium-dependent zinc endoproteinases induced by cytokines and secreted by inflammatory cells. They enhance T-cell migration or adhesion and degrade components of the extracellular matrix proteins. Some MMPs also have been implicated in the formation of β-amyloid. Methods: We examined the expression of MMPs with single and double immunocytochemistry using antibodies against MMP-2, MMP-3, MMP-7, MMP-9, major histocompatibility complex (MHC) class I, CD8+ cells, macrophage, and β-amyloid precursor protein (β-APP) on serial muscle biopsy sections from patients with s-IBM, polymyositis (PM), dermatomyositis (DM), and disease control specimens. The enzyme activity of MMPs was measured by gelatin substrate zymography. Results: Only the gelatinases, MMP-9 and MMP-2, were expressed in the muscle. In s-IBM and PM, but not the control specimens, MMP-9 and MMP-2 immunostained the non-necrotic and MHC class-I-expressing muscle fibers, and MMP-9, but not MMP-2, immunostained the autoinvasive CD8+ cytotoxic T cells. Zymography in muscle homogenates confirmed the increased MMP-2 and MMP-9 enzymatic activity. MMP-2, but not MMP-9, immunostained the rimmed vacuoles in s-IBM and colocalized with β-APP, suggesting a possible involvement with the amyloid deposits. Conclusions.' Because collagen IV is prominent on the muscle membrane, the overexpression of matrix metalloproteinases (MMPs) 2 and 9 on the non-necrotic muscle fibers in polymyositis (PM) and sporadic inclusion body myositis (s-IBM) may facilitate lymphocyte adhesion and enhance T-cell-mediated cytotoxicity by degrading extracellular matrix proteins. The findings may have practical implications in considering therapeutic trials with MMP inhibitors in patients with PM and s-IBM.

Original languageEnglish
Pages (from-to)65-71
Number of pages7
JournalNeurology
Volume54
Issue number1
DOIs
Publication statusPublished - 2000 Jan 11

All Science Journal Classification (ASJC) codes

  • Clinical Neurology

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