Metalloproteinases and their tissue inhibitors in multiple sclerosis

被引:55
作者
Özenci, V [1 ]
Rinaldi, L [1 ]
Teleshova, N [1 ]
Matusevicius, D [1 ]
Kivisäkk, P [1 ]
Kouwenhoven, M [1 ]
Link, H [1 ]
机构
[1] Huddinge Univ Hosp, Dept Neurol, Karolinska Inst, S-14186 Huddinge, Sweden
关键词
metalloproteinases; tissue inhibitors of metalloproteinases; multiple sclerosis; cerebrospinal fluid; in situ hybridization;
D O I
10.1006/jaut.1999.0285
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Matrix metalloproteinases (MMPs) comprise a family of proteolytic enzymes. MMPs are capable of disrupting the blood-brain barrier (BBB), mediating the destruction of extracellular matrix and myelin components. MMPs are also involved in the processing of a:variety of cell surface molecules, including the proinflammatory cytokine TNF-a. Each of these mechanisms are thought to be important in the pathogenesis of multiple sclerosis (MS). We investigated mRNA expression of MMP-3, MMP-9 and two tissue inhibitors of metalloproteinases (TIMP-1 and TIMP-2) in parallel in blood mononuclear cells (MNC) from patients with MS and controls, using in situ hybridization. Numbers of MMP-9 mRNA-expressing cells in blood were higher in patients with MS compared to other neurological diseases (OND), other inflammatory neurological diseases (OIND) and healthy Subjects (P<0.0001 for all comparisons). Patients with MS had also higher levels of MMP-3 and TIMP-1 mRNA expressing blood MNC compared to patients with OND and healthy, subjects. A positive correlation was observed for MMP-9 and TIMP-1 mRNA expression in MS. These results demonstrate that MMPs and TIMPs are upregulated in MS and may contribute to the pathogenesis of the disease. (C) 1999 Academic Press.
引用
收藏
页码:297 / 303
页数:7
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