NF-κB is activated and ICAM-1 gene expression is upregulated during reoxygenation of human brain endothelial cells

Eugene F. Howard, Qiang Chen, Charles Cheng, James E. Carroll, David Hess

Research output: Contribution to journalArticle

72 Scopus citations

Abstract

Reperfusion injury is mediated, in part, by the upregulated expression of genes in microvascular endothelial cells that encode for inflammatory cytokines and adhesion molecules. The redox-regulated transcription factor, nuclear factor kappa B (NF-κB), may play a major role in the induced expression of these genes in this study we use cultured human brain microvascular endothelial cells (HBMEC) to investigate whether reoxygenation of hypoxic HBMEC results in the activation of NF-κB and the upregulation of the adhesion molecule, ICAM-1. When HBMEC were subjected to hypoxia followed by reoxygenation but not hypoxia alone, an NF-κB complex composed of p65 and p50 Rel proteins was rapidly activated within 15-30 min. Four hours later, expression of the ICAM-1 gene was significantly upregulated. The antioxidant pyrrolidine dithiocarbamate and the proteasome inhibitor, n-Tosyl-Phe- chloromethyl ketone, blocked both the activation of NF-κB and the upregulation of the ICAM-1 gene. These results indicate that NF-κB is activated in HBMEC by reoxygenation and may play a significant role in the upregulation of the ICAM-1 gene. Agents which inhibit NF-κB activation may be potential therapeutic agents in acute ischemic stroke.

Original languageEnglish (US)
Pages (from-to)199-203
Number of pages5
JournalNeuroscience Letters
Volume248
Issue number3
DOIs
StatePublished - Jun 5 1998

Keywords

  • Human brain microvascular endothelial cells
  • Hypoxia-reoxygenation
  • ICAM- 1
  • Ischemic stroke
  • Nuclear factor kappa B
  • Reperfusion injury

ASJC Scopus subject areas

  • Neuroscience(all)

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