title: Expression of matrix metalloproteinases in the muscle of patients with inflammatory myopathies.
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 beta-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 beta-amyloid precursor protein (beta-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 beta-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.
authors.affiliation: Neuromuscular Disease Section, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD 20892-1382, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Choi
authors.forename: M C
authors.initials: MC
authors.lastname: Dalakas
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000201:enzymology; D003882:Dermatomyositis / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000473:pathology; D018979:Myositis, Inclusion Body / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D017285:Polymyositis / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology
chemical_list: D016564:Amyloid beta-Protein Precursor; D015395:Histocompatibility Antigens Class I; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9