Effect of acrolein on human alveolar macrophage NF-κB activity

Li Li, Raymond F. Hamilton, Andrij Holian

Research output: Contribution to journalArticlepeer-review

Abstract

Acrolein is an environmental pollutant that is known to suppress respiratory host defense against infections; however, the mechanism of the decrease in host defense is not yet clear. We have previously reported that acrolein inhibited endotoxin-induced cytokine release and induced apoptosis in human alveolar macrophages, suggesting that the inhibition of cytokine release and/or cytotoxicity to alveolar macrophages may, in part, be responsible for acrolein-induced immunosuppression in the lung. Because nuclear factor-κB (NF-κB) is an important transcription factor for a number of cytokine genes and is also an important regulator of apoptosis, the effect of acrolein on NF-κB activity was examined by electrophoresis mobility shift assay. Acrolein caused a dose-dependent inhibition of endotoxin-induced NF- κB activation as well as an inhibition of basal level NF-κB activity. Because IκB is a principal regulator of NF-κB activity in the nucleus, changes in IκB were determined by Western blotting. Acrolein-inhibited IκB phosphorylation leads to an increase in cellular IκB levels preventing NF- κB nuclear transLocation and is likely the mechanism of acrolein-induced inhibition of NF-κB activity. The role of basal level NF-κB in acrolein- induced apoptosis was also examined. An NF-κB inhibitor (MG-132) also induced apoptosis in human alveolar macrophages, suggesting that a certain basal level NF-κB activity may be required for macrophage cell survival. Taken together, our results suggest that the acrolein-inhibited endotoxin- induced NF-κB activation decreased the basal level NF-κB activity, which may be responsible for the inhibition of cytokine release and the induction of apoptosis in human alveolar macrophages.

Original languageEnglish
Pages (from-to)L550-L557
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume277
Issue number3 21-3
DOIs
StatePublished - Sep 1999

Keywords

  • Apoptosis
  • Cytokine
  • IκB
  • MG-132
  • Nuclear factor-κB

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