Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Dose-Response Relationship, Drug
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Gene Expression Regulation
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Humans
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Interferon-beta / pharmacology*
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Interferon-gamma / pharmacology*
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Matrix Metalloproteinase 2 / biosynthesis
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Matrix Metalloproteinase 2 / genetics
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Matrix Metalloproteinases / biosynthesis*
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Matrix Metalloproteinases, Membrane-Associated
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Metalloendopeptidases / biosynthesis
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Metalloendopeptidases / genetics
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Monocytes / drug effects
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Monocytes / enzymology*
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Multiple Sclerosis / enzymology
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RNA, Messenger / biosynthesis
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Tissue Inhibitor of Metalloproteinase-2 / biosynthesis*
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Tissue Inhibitor of Metalloproteinase-2 / genetics
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Transcription, Genetic
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U937 Cells
Substances
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RNA, Messenger
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Tissue Inhibitor of Metalloproteinase-2
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Interferon-beta
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Interferon-gamma
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Matrix Metalloproteinases
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Matrix Metalloproteinases, Membrane-Associated
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Metalloendopeptidases
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Matrix Metalloproteinase 2