Activation of the transcription factor NF-kappa B in human tracheobronchial epithelial cells by inflammatory stimuli

Recent studies have shown that surface epithelial cells play a major role in the defence and inflammatory reactions of the airways. How extracellular stimuli lead to increased gene expression in these epithelial cells is not well known. In this study, we asked whether the multiunit transcription factor, nuclear factor (NF)-kappa B, which regulates the expression of genes involved in defense and immune processes, is activated in airway epithelial cells following stimulation with inflammatory mediators and hydrogen peroxide. In addition, we studied whether this would be followed by upregulation of the NF-kappa B target gene product granulocyte-macrophage colony-stimulating factor (GM-CSF). Activation of NF-kappa B in the SV40 transformed human tracheobronchial epithelial cell line 1HAEo- was measured by electrophoretic mobility shift assays. GM-CSF concentrations in cell culture supernatants were determined by enzyme-linked immunosorbent assays. NF-kappa B was rapidly activated by exposure of cells to interleukin-1 beta (IL-1 beta), phorbol myristate acetate (PMA), and tumour necrosis factor-alpha (TNF). Exposure to H2O2 platelet activating factor (PAF) and lipopolysaccharide (LPS) did not lead to increased NF-kappa B activation. Co-stimulation of IL-1 beta with H2O2 led to augmentation and prolongation of the effect on NF-kappa B activation compared to stimulation with IL-1 beta alone. GM-CSF concentrations increased following stimulation with IL-1 beta and H2O2, and the effect of IL-1 beta/H2O2 co-stimulation on GM-CSF concentrations was additive. These results suggest that NF-kappa B may represent an important transcription factor, controlling the expression of cytokine genes in airway epithelial cells.

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