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-κB activation in endothelial cells

Jeong Ki Min, Young Myeong Kim, Sung Wan Kim, Min Chul Kwon, Young Yun Kong, In Koo Hwang, Moo Ho Won, Jaerang Rho, Young Guen Kwon

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

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-κB. TRANCE induced IκB-α phosphorylation and NF-κB activation via a cascade of reactions involving the TNFR-associated factors, phospholipase C, PI3K, and protein kinase C (PKC-α and PKC-ζ. 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.

Original languageEnglish
Pages (from-to)531-540
Number of pages10
JournalJournal of Immunology
Volume175
Issue number1
Publication statusPublished - 2005 Jul 1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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