Metalloproteinases and their tissue inhibitors in multiple sclerosis

V Ozenci, L Rinaldi, N Teleshova, D Matusevicius, P Kivisäkk, M Kouwenhoven, H Link

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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-alpha. 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.

Original languageEnglish
Pages (from-to)297-303
Number of pages7
JournalJournal of autoimmunity
Issue number4
Publication statusPublished - Jun 1999


  • Adult
  • Aged
  • Collagenases/genetics
  • Female
  • Humans
  • Leukocytes, Mononuclear/metabolism
  • Male
  • Matrix Metalloproteinase 3/genetics
  • Matrix Metalloproteinase 9
  • Middle Aged
  • Multiple Sclerosis/metabolism
  • RNA, Messenger/analysis
  • Tissue Inhibitor of Metalloproteinase-1/genetics
  • Tissue Inhibitor of Metalloproteinase-2/genetics

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