Activation of NF-κB in airway epithelial cells is dependent on CFTR trafficking and Cl- channel function

Adam J. Weber, Grace Soong, Ruth Bryan, Shahryar Saba, Alice Prince

Research output: Contribution to journalReview articlepeer-review

169 Scopus citations


Polymorphonuclear leukocyte-dominated airway inflammation is a major component of cystic fibrosis (CF) lung disease and may be associated with CF transmembrane conductance regulator (CFTR) dysfunction as well as infection. Mutant ΔF508 CFTR is mistrafficked, accumulates in the endoplasmic reticulum (ER), and may cause "cell stress" and activation of nuclear factor (NF)-κB. G551D mutants also lack Cl- channel function, but CFTR is trafficked normally. We compared the effects of CFTR mutations on the endogenous activation of an NF-κB reporter construct. In transfected Chinese hamster ovary cells, the mistrafficked ΔF508 allele caused a sevenfold activation of NF-κB compared with wild-type CFTR or the G551D mutant (P < 0.001). NF-κB was also activated in 9/HTEo-/pCep-R cells and in 16HBE/pcftr antisense cell lines, which lack CFTR Cl- channel function but do not accumulate mutant protein in the ER. This endogenous activation of NF-κB was associated with elevated interleukin-8 expression. Impaired CFTR Cl- channel activity as well as cell stress due to accumulation of mistrafficked CFTR in the ER contributes to the endogenous activation of NF-κB in cells with the CFTR mutation.

Original languageEnglish (US)
Pages (from-to)L71-L78
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number1 25-1
StatePublished - 2001


  • Chloride channel
  • Cystic fibrosis transmembrane conductance regulator
  • Inflammatory response
  • Intracellular calcium
  • Mitogen-activated protein kinase
  • Nuclear factor-κB

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology


Dive into the research topics of 'Activation of NF-κB in airway epithelial cells is dependent on CFTR trafficking and Cl- channel function'. Together they form a unique fingerprint.

Cite this