Interleukin-8 production by cystic fibrosis nasal epithelial cells after tumor necrosis factor-α and respiratory syncytial virus stimulation
Interleukin-8 production by cystic fibrosis nasal epithelial cells after tumor necrosis factor-α and respiratory syncytial virus stimulation
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DOI：
10.1165/ajrcmb.19.2.3053
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发表时间：
1998-08-01
影响因子：
6.4
通讯作者：
Noah, TL
中科院分区：
文献类型：
--
作者：
Black, HR;Yankaskas, JR;Noah, TL
在囊性纤维化 (CF) 患者的气道中观察到高水平的中性粒细胞和中性粒细胞吸引趋化因子白细胞介素 (IL)-8。我们假设 CF 呼吸道上皮在基线或刺激后产生过量的 IL-8。为了检验这一假设，我们比较了用肿瘤坏死因子-α (TNF-α) 刺激培养物或用呼吸道合胞病毒 (RSV) 感染后的几个时间点，由患有或不患有 CF 的幼儿建立的原代鼻上皮细胞 (NEC) 培养物的免疫反应性 IL-8 释放。两种刺激均诱导 CF 和对照培养物显着增加 IL-8 释放。然而，CF细胞和对照细胞之间IL-8反应的强度或持续时间没有差异。还确定了用Ad5-CBCFTR（一种介导囊性纤维化跨膜调节因子（CFTR）表达的腺病毒载体）转导CF细胞对IL-8产生的影响。 TNF-α刺激的IL-8产生在Ad5-CBCFTR转导的、未转导的或Ad5-CMVLacZ转导的对照细胞中没有不同。最后，对永生化 CF 气管上皮细胞系（未校正的和用 CFTR 逆转录病毒校正的）进行了比较。同样，TNF-α 刺激的 IL-8 产生在具有和不具有功能性 CFTR 的细胞系之间没有显着差异。我们的数据表明，在这些条件下培养的分离的 CF NEC 不会比非 CF 对照培养物产生更多的 IL-8，无论是在基线时还是在与非特异性刺激 TNF-α 和 RSV 一起孵育后。我们的结论是，仅功能 CFTR 的缺失不足以导致 IL-8 的过量产生。
High levels of neutrophils and the neutropil-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.