Hemorrhage activates NF-κB in murine lung mononuclear cells in vivo

Robert Shenkar, Michael D. Schwartz, Lance S. Terada, John E. Repine, Joe Mccord, Edward Abraham

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81 Scopus citations

Abstract

Hemorrhage rapidly increases the expression of proinflammatory and immunoregulatory cytokines in the lungs. Binding elements for the nuclear transcriptional regulatory factors (NF)-κB and NF-IL6 (C/EBPβ) are present in the promoter regions of multiple cytokine genes, including those whose expression is increased after blood loss. In the present experiments, we found increased activation in vivo of NF-κB in lung mononuclear cells, but not in splenocytes, taken from mice 1 h after hemorrhage. In contrast, hemorrhage did not activate NF-IL6 in lung cells or splenocytes. Inhibition of xanthine oxidase by prior feeding of a tungsten-enriched diet prevented hemorrhage-induced activation in lung cells of NF-κB. Incubating splenocytes in vitro with xanthine oxidase activated NF-κB but not NF-IL6. Xanthine oxidase-induced activation of NF-κB was inhibited by manganese superoxide dismutase, but not by catalase. These results suggest that xanthine oxidase- mediated superoxide anion-dependent activation of NF-κB occurs in vivo and in vitro. This mechanism may contribute to increased lung cytokine responses after hemorrhage.

Original languageEnglish (US)
Pages (from-to)L729-L735
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume270
Issue number5 14-5
StatePublished - May 1 1996

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Keywords

  • cytokines
  • gene regulation
  • oxygen radicals
  • promoter
  • transcription factors

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Shenkar, R., Schwartz, M. D., Terada, L. S., Repine, J. E., Mccord, J., & Abraham, E. (1996). Hemorrhage activates NF-κB in murine lung mononuclear cells in vivo. American Journal of Physiology - Lung Cellular and Molecular Physiology, 270(5 14-5), L729-L735.