Proinflammatory effects of LIGHT through HVEM and LTbetaR interactions in cultured human umbilical vein endothelial cells.
Members of the tumor necrosis factor (TNF) receptor (TNFR) superfamily are known to be potent mediators of immune responses. LIGHT is a member of the TNF superfamily, and its receptors have been identified as lymphotoxin beta receptor (LTbetaR), herpes virus entry mediator (HVEM), and decoy receptor 3 (DcR3). LIGHT can induce either cell death and/or NF-kappaB activation via its interaction with LTbetaR and/or HVEM. In this study, we investigated the effects of LIGHT in human umbilical vein endothelial cells (HUVECs). We demonstrated that both LTbetaR and HVEM, but not DcR3, are present in HUVECs, and LIGHT can induce the secretion of chemokines (IL-8 and GRO-alpha), cell surface expression of adhesion molecules (ICAM-1 and VCAM-1), PGI2 release, and COX-2 expression. However, the LIGHT mutein, LIGHT-R228E, which has been shown to exhibit binding specificity to LTbetaR, could not induce the secretion of GRO-alpha, PGI2, or the expression of COX-2. These results indicate that both LTbetaR and HVEM can discriminatively mediate the expression of different genes in HUVECs, and suggest that LIGHT is a proinflammatory cytokine.
Chang
Ying Hsin
YH
Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Hsieh
Shie Liang
SL
Chao
Yee
Y
Chou
Yang Chieh
YC
Lin
Wan Wan
WW
D002448:Cell Adhesion; D016923:Cell Death; D002460:Cell Line; D002478:Cells, Cultured; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000096:biosynthesis / Q000378:metabolism; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D011464:Epoprostenol / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D007249:Inflammation; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016209:Interleukin-8 / Q000096:biosynthesis / Q000378:metabolism; D053259:Lymphotoxin beta Receptor; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D053240:Receptors, Tumor Necrosis Factor, Member 14; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D011991:Receptors, Virus / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology*; D015854:Up-Regulation; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000378:metabolism
C475829:CXCL1 protein, human; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D016209:Interleukin-8; C505697:LTBR protein, human; D053259:Lymphotoxin beta Receptor; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D053240:Receptors, Tumor Necrosis Factor, Member 14; D053323:Receptors, Tumor Necrosis Factor, Member 6b; D011991:Receptors, Virus; C506028:TNFRSF14 protein, human; C505911:TNFRSF6B protein, human; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D011464:Epoprostenol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases