Inflammation in cystic fibrosis airways: relationship to increased bacterial adherence

Eur Respir J. 2001 Jan;17(1):27-35. doi: 10.1183/09031936.01.17100270.

Abstract

It is unclear whether inflammation in the cystic fibrosis (CF) lung relates predominantly to bacterial infection, or occurs as a direct consequence of mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein. Interleukin (IL)-8 secretion from CF and non-CF cell lines, and from CF and non-CF human primary nasal epithelial cells incubated with or without Pseudomonas aeruginosa, was measured. Activation of nuclear factor-kappaB (NF-kappaB) in unstimulated CF and non-CF nasal epithelial cells, cell lines and murine tissues was measured by gel-shift assays. No significant difference in basal IL-8 production or NF-kappaB activation was observed between CF and non-CF primary nasal cells. However, CF cells exhibited a significantly (p<0.01) increased IL-8 secretion following P. aeruginosa stimulation. Equalization of the increased P. aeruginosa adherence observed in CF cells, to non-CF levels, resulted in comparable IL-8 secretion. Further, IL-8 production did not differ with mutations which result in either correctly localized CFTR, or in partial/total mislocalization of this protein. Similar levels of NF-kappaB activation were observed in a number of organs of wildtype and CF mice. Finally, IL-8 secretion and NF-kappaB activity were not consistently increased in CF cell lines. Cos-7 cell transfection with plasmids expressing deltaF508 or G551D mutant CFTR protein resulted in increased activation of a p50-containing NF-kappaB complex, but IL-8 secretion was similar to wild-type cells. The authors conclude that the stimulus produced by Pseudomonas aeruginosa is the predominant inflammatory trigger in their models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Bacterial Adhesion / physiology*
  • Bacterial Infections / complications
  • Bacterial Infections / pathology
  • Bronchi / cytology
  • Bronchi / metabolism
  • COS Cells / metabolism
  • Cell Line
  • Cells, Cultured
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / microbiology*
  • Cystic Fibrosis / pathology*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator / physiology*
  • Female
  • Genotype
  • Humans
  • Inflammation
  • Interleukin-8 / biosynthesis*
  • Lung / metabolism
  • Lung / microbiology
  • Lung / pathology*
  • Male
  • Mice
  • Mice, Inbred CFTR
  • Middle Aged
  • Mutation
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Nasal Mucosa / metabolism
  • Nasal Mucosa / microbiology
  • Pseudomonas aeruginosa / physiology*
  • Respiratory Mucosa / metabolism
  • Respiratory Mucosa / microbiology
  • Trachea / cytology
  • Trachea / metabolism
  • Transcriptional Activation
  • Transfection
  • beta-Galactosidase / genetics

Substances

  • CFTR protein, human
  • Interleukin-8
  • NF-kappa B
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • beta-Galactosidase