Involvement of TL1A and DR3 in induction of pro-inflammatory cytokines and matrix metalloproteinase-9 in atherogenesis

• Published in: Cytokine (Philadelphia, Pa.) Pa.), 2005-03, Vol.29 (5), p.229-235
• Main Authors: Kang, Yoon-Joong, Kim, Won-Jung, Bae, Hyung-Uk, Kim, Dong-Ik, Park, Yong Bok, Park, Jeong-Euy, Kwon, Byoung S., Lee, Won-Ha
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Arteriosclerosis - enzymology; Arteriosclerosis - metabolism; Arteriosclerosis - pathology; Atherosclerosis; Cell Line; Cytokines - biosynthesis; Cytokines - metabolism; Foam cells; Humans; Immunohistochemistry; Inflammation - metabolism; Matrix metalloproteinase; Matrix Metalloproteinase 9 - metabolism; Middle Aged; Monocyte; Monocytes - metabolism; Receptors, Tumor Necrosis Factor - metabolism; Receptors, Tumor Necrosis Factor, Member 25; Tumor Necrosis Factor Ligand Superfamily Member 15; Tumor necrosis factor superfamily; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 1043-4666; 1096-0023
• DOI: 10.1016/j.cyto.2004.12.001

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-γ caused induction of pro-atherogenic cytokines/chemokines such as TNF-α, monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-8. Treatment of THP-1 cells with recombinant TL1A in combination with IFN-γ 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.