PMID- 10636127
OWN - NLM
STAT- MEDLINE
DCOM- 20000127
LR  - 20190514
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 54
IP  - 1
DP  - 2000 Jan 11
TI  - Expression of matrix metalloproteinases in the muscle of patients with 
      inflammatory myopathies.
PG  - 65-71
AB  - 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.
FAU - Choi, Y C
AU  - Choi YC
AD  - Neuromuscular Disease Section, National Institute of Neurological Disorders and 
      Stroke, National Institute of Health, Bethesda, MD 20892-1382, USA.
FAU - Dalakas, M C
AU  - Dalakas MC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Histocompatibility Antigens Class I)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Amyloid beta-Protein Precursor/metabolism
MH  - CD8-Positive T-Lymphocytes/enzymology
MH  - Dermatomyositis/*enzymology/metabolism/pathology
MH  - Histocompatibility Antigens Class I/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Matrix Metalloproteinase 2/*metabolism
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Muscle Fibers, Skeletal/metabolism
MH  - Muscle, Skeletal/*enzymology/pathology
MH  - Myositis, Inclusion Body/*enzymology/metabolism/pathology
MH  - Polymyositis/*enzymology/metabolism/pathology
EDAT- 2000/01/15 00:00
MHDA- 2000/01/15 00:01
CRDT- 2000/01/15 00:00
PHST- 2000/01/15 00:00 [pubmed]
PHST- 2000/01/15 00:01 [medline]
PHST- 2000/01/15 00:00 [entrez]
AID - 10.1212/wnl.54.1.65 [doi]
PST - ppublish
SO  - Neurology. 2000 Jan 11;54(1):65-71. doi: 10.1212/wnl.54.1.65.