title: Inflammation in cystic fibrosis airways: relationship to increased bacterial adherence.
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.
authors: Dept. of Gene Therapy, Imperial College at the National Heart and Lung Institute, London, UK.
authors: P
authors: P
authors: Scheid
authors: L
authors: L
authors: Kempster
authors: U
authors: U
authors: Griesenbach
authors: J C
authors: JC
authors: Davies
authors: A
authors: A
authors: Dewar
authors: P P
authors: PP
authors: Weber
authors: W H
authors: WH
authors: Colledge
authors: M J
authors: MJ
authors: Evans
authors: D M
authors: DM
authors: Geddes
authors: E W
authors: EW
authors: Alton
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001422:Bacterial Adhesion / Q000502:physiology*; D001424:Bacterial Infections / Q000150:complications / Q000473:pathology; D001980:Bronchi / Q000166:cytology / Q000378:metabolism; D019556:COS Cells / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003550:Cystic Fibrosis / Q000150:complications / Q000235:genetics / Q000382:microbiology* / Q000473:pathology*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000096:biosynthesis*; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology*; D008297:Male; D051379:Mice; D018181:Mice, Inbred CFTR; D008875:Middle Aged; D009154:Mutation; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009297:Nasal Mucosa / Q000378:metabolism / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D020545:Respiratory Mucosa / Q000378:metabolism / Q000382:microbiology; D014132:Trachea / Q000166:cytology / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D001616:beta-Galactosidase / Q000235:genetics
chemical_list: C505032:CFTR protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D001616:beta-Galactosidase