Abstract
The expression of TWEAK (TNFSF12) and TweakR/Fn14 was detected in regions rich in macrophage/foam cells in atherosclerotic plaques. The role of TWEAK in monocytes in relation to atherogenesis was investigated by analyzing the cellular events induced by TWEAK in a human macrophage-like cell line, THP-1. TWEAK induced various molecular mediators of atherogenesis, such as IL-6, MCP-1, IL-8 and MMP-9, and the induction was augmented by interferon-gamma. TWEAK-induced activation of MMP-9 was mediated by activation of NF-kappaB. These results suggest that TWEAK is involved in atherosclerosis by inducing pro-inflammatory cytokines and extracellular matrix degrading enzymes, which reduce plaque stability.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aged
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Aged, 80 and over
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Apoptosis Regulatory Proteins
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Carotid Stenosis / etiology
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Carotid Stenosis / metabolism*
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Carrier Proteins / genetics
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Carrier Proteins / pharmacology
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Carrier Proteins / physiology*
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Cell Line / metabolism
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Chemokine CCL2 / biosynthesis
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Chemokine CCL2 / genetics
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Cytokine TWEAK
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Cytokines / biosynthesis*
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Cytokines / genetics
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Enzyme Induction / drug effects
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Foam Cells / metabolism
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Gene Expression Profiling
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Humans
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I-kappa B Proteins / metabolism
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Interferon-gamma / pharmacology*
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Interleukins / biosynthesis
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Interleukins / genetics
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Macrophages / drug effects
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Macrophages / metabolism*
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Matrix Metalloproteinase 9 / biosynthesis*
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Matrix Metalloproteinase 9 / genetics
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Middle Aged
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Monocytes / drug effects
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Monocytes / metabolism
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / metabolism
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Proline / analogs & derivatives*
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Proline / pharmacology
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Recombinant Proteins / pharmacology
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Thiocarbamates / pharmacology
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Transcriptional Activation / drug effects
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Tumor Necrosis Factors
Substances
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Apoptosis Regulatory Proteins
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CCL2 protein, human
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Carrier Proteins
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Chemokine CCL2
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Cytokine TWEAK
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Cytokines
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I-kappa B Proteins
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Interleukins
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NF-kappa B
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Recombinant Proteins
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TNFSF12 protein, human
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Thiocarbamates
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Tumor Necrosis Factors
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prolinedithiocarbamate
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Interferon-gamma
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Proline
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Matrix Metalloproteinase 9