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Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis

Leppert, D. ; Ford, J. ; Stabler, G. ; Grygar, C. ; Lienert, C. ; Huber, S. ; Miller, K M. ; Hauser, S L. ; Kappos, L.

In: Brain : a journal of neurology, 1998, vol. 121, no. 12, p. 2327-2334

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    Titre
    • Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis
    Auteur
    • Leppert, D.. Department of Research, University Hospitals, Basel, Switzerland.
    • Ford, J.. Department of Research, University Hospitals, Basel, Switzerland.
    • Stabler, G.. Department of Research, University Hospitals, Basel, Switzerland.
    • Grygar, C.. Department of Research, University Hospitals, Basel, Switzerland.
    • Lienert, C.. Department of Research, University Hospitals, Basel, Switzerland.
    • Huber, S.. Department of Research, University Hospitals, Basel, Switzerland.
    • Miller, K M.. Department of Research, University Hospitals, Basel, Switzerland.
    • Hauser, S L.. Department of Research, University Hospitals, Basel, Switzerland.
    • Kappos, L.. Department of Research, University Hospitals, Basel, Switzerland.
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:295218
    Summary
    Matrix metalloproteinases (MMPs) are a family of endopeptidases capable of enzymatic digestion of subendothelial basement membrane and other components of the extracellular matrix. Expression of MMP-2, -3, -7 and -9 is increased around multiple sclerosis plaques and in brain tissue in experimental allergic encephalomyelitis. To measure quantitatively the expression of these MMPs and their endogenous inhibitors (TIMP-1 and -2), we analysed samples from 52 patients with relapsing-remitting and primary progressive multiple sclerosis by ELISA (enzyme-linked immunosorbent assay) and substrate-gel electrophoresis (zymography). MMP-9 was increased over controls in 100% of relapsing-remitting multiple sclerosis cases, with similar levels detected in relapses and clinically stable phases of disease. In primary progressive multiple sclerosis, MMP-9 was increased in 57% of CSF samples, but concentrations were below those encountered in the relapsing-remitting form. The selective upregulation of MMP-9 suggests that T-cells and macrophages invading the brain parenchyma and the CSF space are the predominant source of MMP-9 in multiple sclerosis. TIMPs and other MMPs (MMP-2 and -3) were not upregulated or not detectable (MMP-7) in CSF of patients with relapsing-remitting and primary progressive multiple sclerosis. The sustained increase of MMP-9 in clinically stable multiple sclerosis supports the concept that multiple sclerosis is associated with ongoing proteolysis that may result in progressive tissue damage. The selective inhibition of MMP-9 could be a useful approach for the prevention of disease progression in multiple sclerosis