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Metalloproteinases and their tissue inhibitors in multiple sclerosis

V Ozenci1, L Rinaldi, N Teleshova

  • 1Division of Neurology, Karolinska Institute, Huddinge University Hospital, Stockholm, Sweden. Volkan.Ozenci@cnsf.ki.se

Journal of Autoimmunity
|May 20, 1999
PubMed

Insights

Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are upregulated in multiple sclerosis (MS) patients. These enzymes may play a role in the development of MS by affecting the blood-brain barrier and myelin.

Area of Science:

  • Neuroimmunology
  • Molecular Biology
  • Enzymology

Background:

  • Matrix metalloproteinases (MMPs) are enzymes that degrade extracellular matrix components.
  • MMPs can disrupt the blood-brain barrier (BBB) and are implicated in neuroinflammation.
  • Their role in the pathogenesis of multiple sclerosis (MS) is under investigation.

Purpose of the Study:

  • To investigate the mRNA expression of MMP-3, MMP-9, TIMP-1, and TIMP-2 in patients with MS.
  • To compare MMP and TIMP expression in blood mononuclear cells (MNCs) between MS patients and controls.

Main Methods:

  • In situ hybridization was used to quantify mRNA expression of MMP-3, MMP-9, TIMP-1, and TIMP-2.
  • Blood mononuclear cells (MNCs) were analyzed from patients with MS, other neurological diseases (OND), other inflammatory neurological diseases (OIND), and healthy subjects.

Main Results:

  • MMP-9 mRNA-expressing cells were significantly higher in MS patients compared to OND, OIND, and healthy subjects (P<0.0001).
  • MMP-3 and TIMP-1 mRNA levels were also elevated in MS patients compared to OND and healthy subjects.
  • A positive correlation was found between MMP-9 and TIMP-1 mRNA expression in MS patients.

Conclusions:

  • Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are upregulated in the blood of individuals with MS.
  • These findings suggest that MMPs and TIMPs may contribute to the pathogenesis of multiple sclerosis.

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