TWEAK can induce pro-inflammatory cytokines and matrix metalloproteinase-9 in macrophages.
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.
Kim
Se-Hwa
SH
Cardiology Division, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Kang
Yoon-Joong
YJ
Kim
Won-Jung
WJ
Woo
Dong-Kyun
DK
Lee
Yoon
Y
Kim
Dong-Ik
DI
Park
Yong Bok
YB
Kwon
Byoung S
BS
Park
Jeong-Euy
JE
Lee
Won-Ha
WH
D000368:Aged; D000369:Aged, 80 and over; D051017:Apoptosis Regulatory Proteins; D016893:Carotid Stenosis / Q000209:etiology / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line / Q000378:metabolism; D018932:Chemokine CCL2 / Q000096:biosynthesis / Q000235:genetics; D000074049:Cytokine TWEAK; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D005487:Foam Cells / Q000378:metabolism; D020869:Gene Expression Profiling; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology*; D007378:Interleukins / Q000096:biosynthesis / Q000235:genetics; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D011392:Proline / Q000031:analogs & derivatives* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000494:pharmacology; D013859:Thiocarbamates / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects; D048069:Tumor Necrosis Factors
D051017:Apoptosis Regulatory Proteins; C111835:CCL2 protein, human; D002352:Carrier Proteins; D018932:Chemokine CCL2; D000074049:Cytokine TWEAK; D016207:Cytokines; D020672:I-kappa B Proteins; D007378:Interleukins; D016328:NF-kappa B; D011994:Recombinant Proteins; C109743:TNFSF12 protein, human; D013859:Thiocarbamates; D048069:Tumor Necrosis Factors; C066229:prolinedithiocarbamate; D007371:Interferon-gamma; D011392:Proline; D020780:Matrix Metalloproteinase 9