Increased NaCl-induced interleukin-8 production by human bronchial epithelial cells is enhanced by the DeltaF508/W1282X mutation of the cystic fibrosis transmembrane conductance regulator gene.
Increased NaCl-induced interleukin-8 production by human bronchial epithelial cells is enhanced by the DeltaF508/W1282X mutation of the cystic fibrosis transmembrane conductance regulator gene.
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DOI：
10.1016/j.cyto.2006.03.003
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发表时间：
2006-03
期刊：
影响因子：
3.8
通讯作者：
Mallory M. Chan;K. Chmura;E. Chan
中科院分区：
文献类型：
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作者：
Mallory M. Chan;K. Chmura;E. Chan
由于对“水合假说”和“盐假说”的理论挑战，描述囊性纤维化（CF）患者气道中气道表面流体（ASF）的满意模型仍有待建立。无论这些模型如何，吸入高渗盐水通常用于促进排出的分泌物的清除。高渗诱导白细胞介素-8（IL-8）表达，这是一种有效的中性粒细胞趋化因子。本研究的目的是：（i）确定三种潜在顺式调节元件在BEAS-2B人支气管上皮细胞中NaCl诱导的IL-8产生的调节中的相对贡献，（ii）比较具有CF跨膜传导调节因子（CFTR）基因的ΔF508/W1282 X突变的IB 3 -1支气管上皮细胞中NaCl诱导的IL-8表达，与C38细胞中的比较，C38细胞是用截短的但有功能的CFTR基因稳定转染的IB 3 -1细胞，和（iii）比较在所有三种细胞类型中诱导IL-8的相等渗透浓度的NaCl和d-山梨醇。在人支气管上皮细胞中，IL-8启动子5′-侧翼区的NFκB、AP-1和NF-IL 6结合位点对于IL-8的最佳NaCl诱导是必需的。具有ΔF508/W1282 X CFTR突变的人支气管上皮细胞产生过量的基础和NaCl诱导的IL-8。
A satisfactory model describing the airway surface fluid (ASF) in the airways of persons with cystic fibrosis (CF) remains to be established due to theoretical challenges to both the “Hydration Hypothesis” and the “Salt Hypothesis.” Irrespective of these models, inhaled hypertonic saline is often used to facilitate clearance of inspissated secretions. Hypertonicity induces interleukin-8 (IL-8) expression, a potent chemokine for neutrophils. The objectives of this study were: (i) to determine the relative contribution of three potential cis-regulatory elements in the regulation of NaCl-induced IL-8 production in BEAS-2B human bronchial epithelial cells, (ii) to compare NaCl-induced IL-8 expression in IB3-1 bronchial epithelial cells, which have the ΔF508/W1282X mutation of the CF transmembrane conductance regulator (CFTR) gene, with that in C38 cells, which are IB3-1 cells stably transfected with a truncated but functional CFTR gene, and (iii) to compare equal osmolar concentrations of NaCl and d-sorbitol in the induction of IL-8 in all three cell types. In human bronchial epithelial cells, binding sites for NFκB, AP-1, and NF-IL6 in the 5′-flanking region of the IL-8 promoter are necessary for optimal NaCl induction of IL-8. Human bronchial epithelial cells with the ΔF508/W1282X CFTR mutation produce an exaggerated amount of basal and NaCl-induced IL-8.