RT Journal Article
SR Electronic
T1 Inflammation in cystic fibrosis airways: relationship to increased bacterial adherence
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 27
OP 35
DO 10.1183/09031936.01.17100270
VO 17
IS 1
A1 P. Scheid
A1 L. Kempster
A1 U. Griesenbach
A1 J.C. Davies
A1 A. Dewar
A1 P.P. Weber
A1 W.H. Colledge
A1 M.J. Evans
A1 D.M. Geddes
A1 E.W.F.W. Alton
YR 2001
UL http://erj.ersjournals.com/content/17/1/27.abstract
AB 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-κB (NF-κB) 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-κB 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-κB activation were observed in a number of organs of wild-type and CF mice. Finally, IL-8 secretion and NF-κB activity were not consistently increased in CF cell lines. Cos-7 cell transfection with plasmids expressing ΔF508 or G551D mutant CFTR protein resulted in increased activation of a p50-containing NF-κB 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.This study was supported by the Association Française de Lutte contre la Mucoviscidose, the Société de Pneumologie de Langue Française, the European Respiratory Society, the North Atlantic Treaty Organization, the Cystic Fibrosis Research Trust and a Wellcome Trust Senior Clinical Fellowship.