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European Respiratory Journal 17:27-35 (2001)
© 2001 ERS Journals Ltd

Inflammation in cystic fibrosis airways: relationship to increased bacterial adherence

P. Scheid1, L. Kempster1, U. Griesenbach1, J.C. Davies1, A. Dewar2, P.P. Weber3, W.H. Colledge4, M.J. Evans5, D.M. Geddes1 and E.W.F.W. Alton1

1 Dept of Gene Therapy, Imperial College at the National Heart and Lung Institute, London, UK, 2 Electron Microscopy and 3 Microbiology Dept, Royal Brompton and Harefield Hospital, 4 Dept of Physiology, University of Cambridge, Cambridge, UK, and 5 School of Biosciences, Cardiff University, Cardiff, UK

CORRESPONDENCE: E.W.F.W. Alton, Dept of Gene Therapy, National Heart and Lung Institute, Manresa Road, London, SW3 6LR, UK. Fax: 44 2073518340

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.

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-{kappa}B (NF-{kappa}B) 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-{kappa}B 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-{kappa}B activation were observed in a number of organs of wild-type and CF mice. Finally, IL-8 secretion and NF-{kappa}B activity were not consistently increased in CF cell lines. Cos-7 cell transfection with plasmids expressing {Delta}F508 or G551D mutant CFTR protein resulted in increased activation of a p50-containing NF-{kappa}B 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.

Keywords: cystic fibrosis trans-membrane conductance regulator, endoplasmic reticulum, interleukin-8, nuclear factor-{kappa}B, Pseudomonas aeruginosa




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