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

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• 作者：Salvatore Carrabino ; Daniela Carpani ; Alessandra Livraghi ; Maurizio Di Cicco ; Diana Costantini ; Elena Copreni ; Carla Colombo and Massimo Conese
• 刊名：Journal of Cystic Fibrosis
• 出版年：2006
• 期刊代码：298_15691993
• 类别：med
• 出版时间：May 2006
• 卷：5
• 期：2
• 页码：113-119
• 文件大小：224 K

摘要

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.