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

Abstract

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.