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Regulation of matrix metalloproteinases and their inhibitors by interferon-β: a longitudinal study in multiple sclerosis patients

Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Düsseldorf, Germany

B Elias

Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Düsseldorf, Germany

HP Hartung

Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Düsseldorf, Germany

BC Kieseier

Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Düsseldorf, Germanybernd.kieseier{at}uni-duesseldorf.de

Background

Matrix metalloproteinases (MMPs) represent a large family of proteolytic enzymes, with some members being implicated in the immunopathogenesis of multiple sclerosis (MS). Interferon (IFN)-β is one of the current mainstays in MS therapy and known to downregulate the expression of MMP-9. However, only sparse information is available on the effects of IFN-β on the other 20 members of the MMP family.

Methods

This is a longitudinal analysis on the RNA expression pattern of all known MMPs and their endogenous inhibitors before and after 1 and 6 months of IFN-β therapy. RNA expression levels were assessed in peripheral venous blood cells from 14 MS patients and 8 matched controls by real time-PCR.

Results

RNA expression levels before treatment differed in part in MS patients compared to healthy controls (MMP-9, MMP-14, MMP-19, TIMP-1, TIMP-2). Some of the MMPs responded to therapy specifically (MMP-8, MMP-9, MMP-19), whereas others remained unchanged over time.

Conclusions

These data suggest that MMPs may differ in their expression levels in MS patients and that this group of enzymes is differentially regulated during the treatment with IFN-β in MS for at least 6 months.

Key Words: disease modifying therapies • immunology • interferon-β • metalloproteinases • multiple sclerosis • tissue inhibitors of metalloproteinases • treatment

This version was published on June 1, 2009

Multiple Sclerosis, Vol. 15, No. 6, 721-727 (2009)
DOI: 10.1177/1352458509102920


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