Exaggerated activation of nuclear factor-kappaB and altered IkappaB-beta processing in cystic fibrosis bronchial epithelial cells

Am J Respir Cell Mol Biol. 2000 Sep;23(3):396-403. doi: 10.1165/ajrcmb.23.3.3949.


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)-kappaB pathway occurs in CF epithelial cells and results in excessive generation of inflammatory cytokines, we evaluated tumor necrosis factor (TNF)-alpha-induced production of the NF-kappaB-dependent cytokine interleukin (IL)-8 and activation of NF-kappaB 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 TNF-alpha (30 ng/ml) resulted in markedly elevated NF-kappaB activation and production of IL-8 by IB3 cells compared with BEAS and C38 cells. Despite the differences in NF- kappaB activation, no differences in basal levels of IkappaB-alpha or TNF-alpha- induced IkappaB-alpha processing and degradation were detected among the cell lines. In contrast, the basal level of IkappaB-beta was increased in the IB3 cells. Treatment with TNF-alpha resulted in increased formation of hypophosphorylated IkappaB-beta and increased nuclear localization of IkappaB-beta in IB3 cells compared with the other cell types. These findings provide additional evidence of a dysregulated inflammatory response in CF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Bronchi / cytology
  • Bronchi / immunology
  • Bronchi / metabolism
  • Cells, Cultured
  • Cystic Fibrosis / immunology*
  • Cystic Fibrosis / metabolism*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Gene Expression / immunology
  • Humans
  • I-kappa B Proteins / immunology
  • I-kappa B Proteins / metabolism*
  • Immunoblotting
  • Interleukin-8 / metabolism
  • Ligases / metabolism
  • Mutagenesis / physiology
  • NF-kappa B / immunology
  • NF-kappa B / metabolism*
  • Phosphorylation
  • Respiratory Mucosa / cytology
  • Respiratory Mucosa / immunology
  • Respiratory Mucosa / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology


  • CFTR protein, human
  • I-kappa B Proteins
  • Interleukin-8
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Ligases
  • guanosine 3',5'-polyphosphate synthetases