Regulation of matrix metalloproteinases and their inhibitors by interferon-beta: 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)-beta 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-beta 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-beta 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-beta in MS for at least 6 months.