Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis.
TL1A (VEGI/TNFSF15) is the ligand for DR3 (TNFRSF12) and is a newly identified member of the tumor necrosis factor superfamily (TNFSF). Previously, DR3 has been shown to have a role in atherogenesis through stimulation of matrix degrading enzymes including matrix metalloproteinase (MMP)-9. Immunohistochemical staining of human carotid atherosclerotic plaques revealed a high-level expression of TL1A in regions rich in macrophage/foam cells. To investigate the role of TL1A and DR3 in the functioning of macrophage/foam cells in relation to atherogenesis, we have analyzed cellular events mediated by TL1A and DR3 in a human macrophage-like cell line, THP-1. Treatment of THP-1 cells with immobilized anti-DR3 monoclonal antibody in combination with IFN-gamma caused induction of pro-atherogenic cytokines/chemokines such as TNF-alpha, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8. Treatment of THP-1 cells with recombinant TL1A in combination with IFN-gamma also caused induction of MMP-9 and IL-8. Furthermore, the expression of DR3 in peripheral blood monocytes was induced after atherogenic stimulation. These data suggest that TL1A and DR3 is involved in atherosclerosis via the induction of pro-inflammatory cytokines/chemokines and decreasing plaque stability by inducing extracellular matrix degrading enzymes.
Kang
Yoon-Joong
YJ
Department of Genetic Engineering, Kyungpook National University, Taegu 702-701, Republic of Korea.
Kim
Won-Jung
WJ
Bae
Hyung-Uk
HU
Kim
Dong-Ik
DI
Park
Yong Bok
YB
Park
Jeong-Euy
JE
Kwon
Byoung S
BS
Lee
Won-Ha
WH
D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053219:Receptors, Tumor Necrosis Factor, Member 25; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016207:Cytokines; D018124:Receptors, Tumor Necrosis Factor; D053219:Receptors, Tumor Necrosis Factor, Member 25; C506033:TNFRSF25 protein, human; C117026:TNFSF15 protein, human; D053380:Tumor Necrosis Factor Ligand Superfamily Member 15; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9