Cystic Fibrosis Bronchial Epithelial Cells
نویسندگان
چکیده
In cystic fibrosis (CF), inflammatory mediator production by airway epithelial cells is a critical determinant of chronic airway inflammation. To determine whether altered signal transduction through the nuclear factor (NF)k B pathway occurs in CF epithelial cells and results in excessive generation of inflammatory cytokines, we evaluated tumor necrosis factor (TNF)a –induced production of the NFk B–dependent cytokine interleukin (IL)-8 and activation of NFk B in three different human bronchial epithelial cell lines: ( 1 ) BEAS cells that express wild-type CF transmembrane conductance regulator (CFTR), ( 2 ) IB3 cells with mutant CFTR, and ( 3 ) C38 cells, which are “corrected” IB3 cells complemented with wild-type CFTR. Treatment of cells with TNFa (30 ng/ml) resulted in markedly elevated NFk B activation and production of IL-8 by IB3 cells compared with BEAS and C38 cells. Despite the differences in NFk B activation, no differences in basal levels of I k Ba or TNFa – induced I k Ba processing and degradation were detected among the cell lines. In contrast, the basal level of I k Bb was increased in the IB3 cells. Treatment with TNFa resulted in increased formation of hypophosphorylated I k Bb and increased nuclear localization of I k Bb in IB3 cells compared with the other cell types. These findings provide additional evidence of a dysregulated inflammatory response in CF.
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تاریخ انتشار 2000