The aim of this study was to elucidate the redox regulation of cytokine-induced NF-κB activation and NF-κB mediated gene induction in A549 cells and primary cultures of human airway epithelial cells. In A549 cells, Western blot analysis showed transient depletion of IκBα
after 15 min IL-1β treatment followed by its reappearance after 60 min, indicating efficient NF-κB-driven gene induction. A similar pattern was observed in primary epithelial cells however, the kinetics were slower and depletion was less. In primary airway epithelial cells IκBα
levels were 59.8±8.5% of control following 30 min treatment with IL-1β and in A549 cells 29.1±8.5% of control following 15 min IL-1β treatment. Cytokine-induced IκBα depletion was associated with NF-κB nuclear accumulation and subsequent resynthesis
of IκBα and upregulation of ICAM-1 in both cell types. The antioxidant, NAC (20 mM) had no effect on the kinetics of cytokine-induced IκBα depletion or NF-κB p65 nuclear translocation in either cell type and failed to influence κB dependent IκBα
resynthesis. H2O2 treatment alone or in combination with cytokines had no significant effects on IκBα depletion, NF-κB p65 nuclear translocation or ICAM-1 expression in either cell type but did cause significant activation of p38 MAPK. These results suggest that cytokine-induced
NF-κB activation in cultured human airway epithelial cells does not involve an NAC-sensitive oxidant stress and that H2O2-induced oxidant stress does not result in effective NF-κB activation and NF-κB mediated gene induction.
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Document Type: Research Article
Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Heart Science Centre, Royal Brompton and Harefield NHS Trust, Harefield, Middlesex, UB9 6JH, UK
Publication date: January 1, 2002
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The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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