Black H R, Yankaskas J R, Johnson L G, Noah T L
Departments of Pediatrics and Internal Medicine, Division of Pulmonary Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Am J Respir Cell Mol Biol. 1998 Aug;19(2):210-5. doi: 10.1165/ajrcmb.19.2.3053.
High levels of neutrophils and the neutrophil-attracting chemokine interleukin (IL)-8 have been observed in the airways of patients with cystic fibrosis (CF). We hypothesized that CF respiratory epithelium produces excessive amounts of IL-8 either at baseline or after stimulation. To test this hypothesis we compared immunoreactive IL-8 release by primary nasal epithelial cell (NEC) cultures established from young children with or without CF, at several time points after stimulation of cultures with tumor necrosis factor-alpha (TNF-alpha) or infection with respiratory syncytial virus (RSV). Both stimuli induced significantly increased IL-8 release by both CF and control cultures. However, there was no difference between CF and control cells in either the magnitude or duration of the IL-8 response. The effect of transduction of CF cells with Ad5-CBCFTR, an adenovirus vector mediating expression of cystic fibrosis transmembrane regulator (CFTR), on IL-8 production was also determined. TNF-alpha stimulated IL-8 production was not different in Ad5-CBCFTR-transduced, -untransduced, or Ad5-CMVLacZ-transduced control cells. Lastly, immortalized CF tracheal epithelial cell lines, both uncorrected and retrovirally corrected with CFTR, were compared. Again, TNF-alpha-stimulated IL-8 production did not differ significantly between cell lines with and without functioning CFTR. Our data suggest that isolated CF NECs cultured under these conditions do not produce more IL-8 than do non-CF control cultures, either at baseline or after incubation with the nonspecific stimuli TNF-alpha and RSV. We conclude that the absence of functioning CFTR alone is not sufficient to cause excessive production of IL-8.
在囊性纤维化（CF）患者的气道中已观察到高水平的中性粒细胞和吸引中性粒细胞的趋化因子白细胞介素（IL）-8。我们推测CF呼吸道上皮细胞在基线时或受到刺激后会产生过量的IL-8。为了验证这一假设，我们比较了来自患有或未患有CF的幼儿的原代鼻上皮细胞（NEC）培养物在肿瘤坏死因子-α（TNF-α）刺激或呼吸道合胞病毒（RSV）感染后的几个时间点的免疫反应性IL-8释放情况。两种刺激均导致CF和对照培养物中IL-8释放显著增加。然而，CF细胞和对照细胞在IL-8反应的幅度或持续时间上没有差异。还确定了用腺病毒载体Ad5-CBCFTR（介导囊性纤维化跨膜调节因子（CFTR）表达）转导CF细胞对IL-8产生的影响。在Ad5-CBCFTR转导、未转导或Ad5-CMVLacZ转导的对照细胞中，TNF-α刺激的IL-8产生没有差异。最后，比较了未校正和用CFTR进行逆转录病毒校正的永生化CF气管上皮细胞系。同样，在具有和不具有功能性CFTR的细胞系之间，TNF-α刺激的IL-8产生没有显著差异。我们的数据表明，在这些条件下培养的分离的CF NECs在基线时或与非特异性刺激物TNF-α和RSV孵育后，产生的IL-8并不比非CF对照培养物多。我们得出结论，仅缺乏功能性CFTR不足以导致IL-8的过量产生。
