Cytokine secretion by cystic fibrosis airway epithelial cells
Cytokine secretion by cystic fibrosis airway epithelial cells
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DOI：
10.1164/rccm.200207-765oc
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发表时间：
2004-03-01
影响因子：
24.7
通讯作者：
Randell, SH
中科院分区：
文献类型：
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作者：
Becker, MN;Sauer, MS;Randell, SH
囊性纤维化跨膜传导调节因子的突变是否在本质上使炎症失调是有争议的。我们的特点是第2代人气管支气管上皮细胞培养的形态学和生理学，并确定是否细胞因子的产生或核因子-kappaB激活囊性纤维化（CF）细胞系统性改变。分别来自总共33个和25个肺的非CF和CIF细胞可用于在塑料上或在空气-液体界面处培养，直到分化良好。毛喉素刺激的短路电流存在于代表性的极化非CIF文化，并在CIF文化缺席，而尿苷5 '-三磷酸刺激的电流都存在。非CF和CIF细胞之间的组成性或白细胞介素（IL）-1 β诱导的IL-8或IL-6分泌或核因子-κ B活性没有显著差异。未检测到活化后调节的正常T细胞表达和分泌的细胞因子（RANTES）和IL-10。用肿瘤坏死因子-α或合成的Toll样受体2激动剂或不同剂量和时间的金黄色葡萄球菌培养滤液刺激，显示CIF细胞产生IL-8的单一剂量和时间依赖性差异。有趣的是，虽然在不存在人血清的情况下，用铜绿假单胞菌刺激后，CIF细胞中的IL-8分泌并不更大，但在其存在下，IL-8分泌却更大。因此，尽管在某些条件下可能会产生过度反应，但我们的结果不支持CIF细胞中的整体固有高炎症表型。
It is controversial whether mutations in cystic fibrosis transmembrane conductance regulator intrinsically dysregulate inflammation. We characterized passage 2 human tracheobronchial epithelial cell cultures morphologically and physiologically and determined whether cytokine production or nuclear factor-kappaB activation was systematically altered in cystic fibrosis (CF) cells. Non-CF and CIF cells originating from a total of 33 and 25 lungs, respectively, were available for culture on plastic or at an air-liquid interface until well differentiate. Forskolin-stimulated short-circuit currents were present in representative polarized non-CIF cultures and were absent in CIF cultures, whereas uridine 5'-triphosphate-stimulated currents were present in both. Constitutive or interleukin (IL)-1beta-induced IL-8 or IL-6 secretion or nuclear factor-kappaB activity was not significantly different between non-CF and CIF cells. The cytokines regulated upon activation, normal T cell expressed and secreted (RANTES) and IL-10 were not detectable. Stimulation with tumor necrosis factor-alpha or a synthetic toll-like receptor 2 agonist or variable doses and times of Staphylococcus aureus culture filtrate revealed a single dose- and time-dependent difference in IL-8 production by CIF cells. Interestingly, although IL-8 secretion after stimulation with Pseudomonas aeruginosa filtrates was not greater in CIF cells in the absence of human serum, it was variably greater in its presence. Thus, although exaggerated responses may develop under certain conditions, our results do not support an overall intrinsically hyperinflammatory phenotype in CIF cells.