Regulation of matrix metalloproteinases and their inhibitors by interferon-beta: a longitudinal study in multiple sclerosis patients.
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.
Bernal
F
F
Department of Neurology, Research Group for Clinical and Experimental Neuroimmunology, Heinrich-Heine-University, Düsseldorf, Germany.
Elias
B
B
Hartung
H P
HP
Kieseier
B C
BC
D000328:Adult; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D066298:In Vitro Techniques; D016899:Interferon-beta / Q000627:therapeutic use*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008137:Longitudinal Studies; D008297:Male; D053511:Matrix Metalloproteinase 14 / Q000235:genetics; D020784:Matrix Metalloproteinase 8 / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000235:genetics*; D053505:Matrix Metalloproteinases, Secreted / Q000235:genetics; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
D007155:Immunologic Factors; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D016899:Interferon-beta; D020782:Matrix Metalloproteinases; D053505:Matrix Metalloproteinases, Secreted; C108362:matrix metalloproteinase 19; D020784:Matrix Metalloproteinase 8; D020780:Matrix Metalloproteinase 9; D053511:Matrix Metalloproteinase 14