Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor α in endothelium

Toshiyuki Arai, Susan A. Kelly, Matthew L. Brengman, Manabu Takano, Elise H. Smith, Pascal J. Goldschmidt-Clermont, Gregory B. Bulkley

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Proinflammatory cytokines upregulate endothelial adhesion molecule expression, thereby initiating the microvascular inflammatory response. We re-evaluated the reported role of reactive oxygen metabolites (ROMs) in signalling upregulation of intercellular adhesion molecule 1 (ICAM-1) on endothelial cells by tumour necrosis factor α (TNF-α) in vitro. TNF-α upregulation of endothelial-cell ICAM-1 expression was inhibited by the cell-permeable antioxidants, or by the adenovirus-mediated intracellular overexpression of Cu,Zn-superoxide dismutase, but not by the exogenous (extracellular) administration of the cell-impermeable antioxidants, superoxide dismutase and/or catalase. This ICAM-1 upregulation was also inhibited by inhibitors of NADH dehydrogenase, cytochrome bc1 complex and NADPH oxidase. However, a measurable increase in net cellular ROM generation in response to TNF-α was not seen using four disparate sensitive ROM assays. Moreover, the stimulation of exogenous or endogenous ROM generation did not upregulate ICAM-1, nor enhance ICAM-1 upregulation by TNF-α. These findings suggest that an ambient background flux of ROMs, generated intracellularly, but not their net incremental generation, is necessary for TNF-α to induce ICAM-1 expression in endothelium in vitro.

Original languageEnglish (US)
Pages (from-to)853-861
Number of pages9
JournalBiochemical Journal
Volume331
Issue number3
DOIs
StatePublished - May 1 1998

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Arai, T., Kelly, S. A., Brengman, M. L., Takano, M., Smith, E. H., Goldschmidt-Clermont, P. J., & Bulkley, G. B. (1998). Ambient but not incremental oxidant generation effects intercellular adhesion molecule 1 induction by tumour necrosis factor α in endothelium. Biochemical Journal, 331(3), 853-861. https://doi.org/10.1042/bj3310853