Modulation of monocytes matrix metalloproteinase-2, MT1-MMP and TIMP-2 by interferon-gamma and -beta: implications to multiple sclerosis.
Recent findings have implicated the activity of matrix metalloproteinases (MMPs) in the pathogenesis of multiple sclerosis (MS), while in vivo interferon (IFN)-beta treatment was demonstrated to suppress MMPs. In the present study, the effects mediated by IFN-gamma and IFN-beta on the mRNA and protein expression of MMP-2, its physiological activator, MT1-MMP and its endogenous inhibitor, TIMP-2, by monocytes were evaluated in vitro. The results point to the significance of IFNs in modulating MMPs/tissue inhibitors of MMPs (TIMPs) expression, and support the possibility that the therapeutic effects of IFN-beta may be, in part, due to induction of a shift from "pro-" to "anti-proteolytic" pattern of MMPs and TIMPs expression.
Galboiz
Yanina
Y
Neuroimmunology Unit, Department of Neurology, Carmel Medical Center, 7 Michal Street, Haifa, Israel.
Shapiro
Sarah
S
Lahat
Nitza
N
Miller
Ariel
A
D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D016899:Interferon-beta / Q000494:pharmacology*; D007371:Interferon-gamma / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000096:biosynthesis / Q000235:genetics; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology*; D009103:Multiple Sclerosis / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D020298:U937 Cells
D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D016899:Interferon-beta; D007371:Interferon-gamma; D020782:Matrix Metalloproteinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2