TWEAK Can Induce Pro-Inflammatory Cytokines and Matrix Metalloproteinase-9 in Macrophages

• Published in: Circulation Journal 2004, Vol.68(4), pp.396-399
• Main Authors: Kim, Se-Hwa, Kang, Yoon-Joong, Kim, Won-Jung, Woo, Dong-Kyun, Lee, Yoon, Kim, Dong-Ik, Park, Yong Bok, Kwon, Byoung S., Park, Jeong-Euy, Lee, Won-Ha
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Apoptosis Regulatory Proteins; Atherosclerosis; Carotid Stenosis - etiology; Carotid Stenosis - metabolism; Carrier Proteins - genetics; Carrier Proteins - pharmacology; Carrier Proteins - physiology; Cell Line - metabolism; Chemokine CCL2 - biosynthesis; Chemokine CCL2 - genetics; Cytokine TWEAK; Cytokines - biosynthesis; Cytokines - genetics; Enzyme Induction - drug effects; Foam cells; Foam Cells - metabolism; Gene Expression Profiling; Humans; I-kappa B Proteins - metabolism; Interferon-gamma - pharmacology; Interleukins - biosynthesis; Interleukins - genetics; Macrophages - drug effects; Macrophages - metabolism; Matrix Metalloproteinase 9 - biosynthesis; Matrix Metalloproteinase 9 - genetics; Middle Aged; Monocytes - drug effects; Monocytes - metabolism; NF-kappa B - antagonists & inhibitors; NF-kappa B - metabolism; Proline - analogs & derivatives; Proline - pharmacology; Recombinant Proteins - pharmacology; Thiocarbamates - pharmacology; Transcriptional Activation - drug effects; Tumor Necrosis Factors; TWEAK
• ISSN: 1346-9843; 1347-4820
• DOI: 10.1253/circj.68.396

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-γ. TWEAK-induced activation of MMP-9 was mediated by activation of NF-κB. These results suggest that TWEAK is involved in atherosclerosis by inducing pro-inflammatory cytokines and extracellular matrix degrading enzymes, which reduce plaque stability. (Circ J 2004; 68: 396 - 399)