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-κB activity in primary respiratory epithelial cells cultured from nasal polyps obtained from CF and non-CF subjects. Methods: NF-κB 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-κB than non-CF cells (P = 0.0004). P. aeruginosa challenge and IL-1β/H2O2 co-stimulation caused four and two fold induction of NF-κB 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-1β/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-κB activity. Our data corroborate the hypothesis of a basal exaggerated inflammatory response in the CF respiratory epithelium.

Dysregulated interleukin-8 secretion and NF-kappaB activity in human cystic fibrosis nasal epithelial cells / S. Carrabino, D. Carpani, A. Livraghi, M. Di Cicco, D. Costantini, E. Copreni, C. Colombo, M. Conese. - In: JOURNAL OF CYSTIC FIBROSIS. - ISSN 1569-1993. - 5:2(2006), pp. 113-119. [10.1016/j.jcf.2005.12.003]

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

D. Costantini;C. Colombo
Penultimo
;
2006

Abstract

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-κB activity in primary respiratory epithelial cells cultured from nasal polyps obtained from CF and non-CF subjects. Methods: NF-κB 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-κB than non-CF cells (P = 0.0004). P. aeruginosa challenge and IL-1β/H2O2 co-stimulation caused four and two fold induction of NF-κB 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-1β/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-κB activity. Our data corroborate the hypothesis of a basal exaggerated inflammatory response in the CF respiratory epithelium.
Settore MED/38 - Pediatria Generale e Specialistica
2006
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/31046
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