TNF-related activation-induced cytokine enhances leukocyte adhesiveness: induction of ICAM-1 and VCAM-1 via TNF receptor-associated factor and protein kinase C-dependent NF-kappaB activation in endothelial cells.
Inflammation is a basic pathological mechanism leading to a variety of vascular diseases. The inflammatory reaction involves complex interactions between both circulating and resident leukocytes and the vascular endothelium. In this study, we report evidence for a novel action of TNF-related activation-induced cytokine (TRANCE) as an inflammatory mediator and its underlying signaling mechanism in the vascular wall. TRANCE significantly increased endothelial-leukocyte cell interactions, and this effect was associated with increased expression of the cell adhesion molecules, ICAM-1 and VCAM-1, on the endothelial cells. RT-PCR analysis and promoter assays revealed that expression of these cell adhesion molecules was transcriptionally regulated mainly by activation of the inflammatory transcription factor, NF-kappaB. TRANCE induced IkappaB-alpha phosphorylation and NF-kappaB activation via a cascade of reactions involving the TNFR-associated factors, phospholipase C, PI3K, and protein kinase C (PKC-alpha and PKC-zeta). It also led to the production of reactive oxygen species via PKC- and PI3K-dependent activation of NADPH oxidase in the endothelial cells, and antioxidants suppressed the responses to TRANCE. These results demonstrate that TRANCE has an inflammatory action and may play a role in the pathogenesis of inflammation-related diseases.
Department of Biochemistry, College of Sciences, Yonsei University, Seoul, Republic of Korea.
Jeong-Ki
JK
Min
Young-Myeong
YM
Kim
Sung Wan
SW
Kim
Min-Chul
MC
Kwon
Young-Yun
YY
Kong
In Koo
IK
Hwang
Moo Ho
MH
Won
Jaerang
J
Rho
Young-Guen
YG
Kwon
D001483:Base Sequence; D002352:Carrier Proteins / Q000276:immunology* / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000276:immunology* / Q000494:pharmacology; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D047992:TNF Receptor-Associated Factor 2 / Q000235:genetics / Q000378:metabolism; D048029:TNF Receptor-Associated Factor 6 / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D020298:U937 Cells; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
D002352:Carrier Proteins; D020672:I-kappa B Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D053245:RANK Ligand; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D053246:Receptor Activator of Nuclear Factor-kappa B; D011994:Recombinant Proteins; D047992:TNF Receptor-Associated Factor 2; D048029:TNF Receptor-Associated Factor 6; C505686:TNFRSF11A protein, human; C505688:TNFSF11 protein, human; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D000072000:NF-KappaB Inhibitor alpha; D004247:DNA; D011493:Protein Kinase C