Metalloproteinases and their tissue inhibitors in multiple sclerosis

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 i nvolved in the processing of a:variety of cell surface molecules, including the proinflammatory cytokine TNF-a. Each of these mechanisms are thought t o be important in the pathogenesis of multiple sclerosis (MS). We investiga ted mRNA expression of MMP-3, MMP-9 and two tissue inhibitors of metallopro teinases (TIMP-1 and TIMP-2) in parallel in blood mononuclear cells (MNC) f rom patients with MS and controls, using in situ hybridization. Numbers of MMP-9 mRNA-expressing cells in blood were higher in patients with MS compar ed to other neurological diseases (OND), other inflammatory neurological di seases (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 M NC compared to patients with OND and healthy, subjects. A positive correlat ion 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.