Dysregulated interleukin-8 secretion and NF-κB activity in human cystic fibrosis nasal epithelial cells

Background: It is not clear whether cystic fibrosis (CF) airway inflammation is a consequence of bacterial infection or is intrinsically dysregulated. The aim of this study was to investigate IL-8 secretion and NF-kappa B activity in primary respiratory epithelial cells cultured from nasal polyps obtained from CF and non-CF subjects. Methods: NF-kappa B activity was studied by electrophoretic mobility-shift and quantitative colorimetric assays in nuclear extracts. Immunoreactive IL-8 levels were assessed by ELISA in cell culture supernatants. Both parameters were studied at baseline and following challenge with Pseudomonas aeruginosa or stimulation with pro-inflammatory cytokines. Results: Under basal conditions, CF cells presented a significant higher activity of NF-kappa B than non-CF cells (P=0.0004). R aeruginosa challenge and IL-1 beta/H2O2 co-stimulation caused four and two fold induction of NF-kappa B activity in non-CF and CF cells, respectively. IL-8 levels in unstimulated CF cells were significantly higher than in non-CF cells (P=0.0025). Upon incubation with P aeruginosa and IL-1 beta/ H2O2, non-CF cells produced 6.3 times more IL-8 than unstimulated cells, whereas IL-8 secretion increased only of 1.4 times in CF cells. Conclusions: CF respiratory epithelial cells exhibit a basal dysregulated production of IL-8 that partially correlates to enhanced NF-kappa B activity. Our data corroborate the hypothesis of a basal exaggerated inflammatory response in the CF respiratory epithelium. (C) 2006 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.