Hyperoxia prolongs tumor necrosis factor-α-mediated activation of Nf-κB: Role of IκB kinase

Hector R. Wong*, Kelli K. Odoms, Alvin G. Denenberg, Geoffrey L. Allen, Thomas P. Shanley

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Hyperoxia and tumor necrosis factor-α (TNFα) are two canonical signals centrally involved in the patho-physiology of acute lung injury. We have attempted to elucidate the effects of these two stimuli on the signal transduction pathways of lung parenchymal cells. In cultured human lung epithelial cells, exposure to hyperoxia alone (95% oxygen) did not affect NF-κB activation or degradation of the NF-κB inhibitory protein, IκBα. Stimulation with TNFα alone increased NF-κB activation within 1 h and induced IκBα degradation within 0.5 h. After TNFα alone, NF-κB activation returned to baseline within 2 h and this corresponded with near complete IκBα resynthesis within 1 h of stimulation. In contrast, simultaneous exposure to hyperoxia and TNFα prolonged NF-κB activation up to 7 h, and IκBα degradation up to 2 h after stimulation. Hyperoxia did not affect TNFα-mediated resynthesis of IκBα mRNA. Hyperoxia alone did not induce IκB kinase (IKK) activity, but significantly prolonged TNFα-mediated activation of IKK activity. Hyperoxia alone did not activate the intercellular adhesion molecule-1 (ICAM-1) promoter, but augmented TNFα-mediated activation of the ICAM-1 promoter. These data demonstrate that while hyperoxia alone does not affect activation of NF-κB, hyperoxia prolongs TNFα-mediated activation of NF-κB. The mechanism of this effect involves, in part, prolonged degradation of IκBα resulting from prolonged activation of IKK.

Original languageEnglish (US)
Pages (from-to)274-279
Number of pages6
JournalShock
Volume17
Issue number4
DOIs
StatePublished - Apr 2002

Keywords

  • Inflammation
  • Lung injury
  • Oxidants
  • Signal transduction
  • Transcription factor

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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