鼻病毒感染对人鼻腔黏膜囊性纤维化跨膜电导调节因子和上皮钠通道表达和功能的影响。
Effects of rhinovirus infection on the expression and function of cystic fibrosis transmembrane conductance regulator and epithelial sodium channel in human nasal mucosa.
机构信息
Department of Otorhinolaryngology-Head and Neck Surgery, Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Chuncheon, South Korea.
出版信息
Ann Allergy Asthma Immunol. 2012 Mar;108(3):182-7. doi: 10.1016/j.anai.2011.12.018. Epub 2012 Jan 26.
BACKGROUND
Changes in expression and function of the cystic fibrosis transmembrane conductance regulator (CFTR) and epithelial sodium channel (ENaC) have been found to cause airway surface liquid (ASL) derangement and to impair mucociliary clearance, both of which have been linked to the pathogenesis of rhinovirus (RV) infection.
OBJECTIVES
The effects of RV infection on the expression and function of CFTR and ENaC in nasal epithelial cells were investigated.
METHODS
Nasal epithelial cells obtained from 14 turbinoplasty patients were infected with RV serotype 16 (RV-16) for 4 hours. Expression of CFTR, α-ENaC, β-ENaC, and γ-ENaC was determined by real-time polymerase chain reaction, Western blot analysis, and confocal immunofluorescence microscopy. Functional changes in the CFTR and ENaC proteins were assessed by measuring transepithelial resistance (TER) using a voltmeter combined with ion channel modulators.
RESULTS
Rhinovirus infection increased expression of CFTR, α-ENaC, β-ENaC, and γ-ENaC messenger RNA (mRNA) and protein compared with controls (P < .05 each) and increased the expression of all 4 proteins on confocal immunofluorescence microscopy. Treatment of cells with the ENaC blocker amiloride and the CFTR activator forskolin increased TER in RV-infected cells, whereas forskolin decreased TER in uninfected cells. The CFTR inhibitor NPPB, however, blocked CFTR more in RV-infected than in noninfected cells.
CONCLUSIONS
Rhinovirus increased the expression of CFTR and appeared to alter its function. In contrast, ENaC expression and function were increased by RV infection. Therefore, RV infection may impair mucociliary transport of nasal epithelium by these alterations.
背景
囊性纤维化跨膜电导调节因子（CFTR）和上皮钠离子通道（ENaC）的表达和功能变化已被发现导致气道表面液体（ASL）紊乱，并损害黏液纤毛清除功能，这两者都与鼻病毒（RV）感染的发病机制有关。
目的
研究 RV 感染对鼻上皮细胞 CFTR 和 ENaC 表达和功能的影响。
方法
从 14 例鼻整形术患者中获取鼻上皮细胞，用 RV 血清型 16（RV-16）感染 4 小时。通过实时聚合酶链反应、Western blot 分析和共聚焦免疫荧光显微镜检测 CFTR、α-ENaC、β-ENaC 和 γ-ENaC 的表达。通过使用伏特计结合离子通道调节剂测量跨上皮电阻（TER）来评估 CFTR 和 ENaC 蛋白的功能变化。
结果
RV 感染与对照组相比，增加了 CFTR、α-ENaC、β-ENaC 和 γ-ENaC 信使 RNA（mRNA）和蛋白的表达（均 P <.05），并在共聚焦免疫荧光显微镜上增加了所有 4 种蛋白的表达。用 ENaC 阻断剂阿米洛利和 CFTR 激活剂 forskolin处理细胞可增加 RV 感染细胞中的 TER，而 forskolin 降低未感染细胞中的 TER。然而，CFTR 抑制剂 NPPB 在 RV 感染细胞中对 CFTR 的阻断作用强于未感染细胞。
结论
RV 增加了 CFTR 的表达，并似乎改变了其功能。相比之下，ENaC 的表达和功能增加是由 RV 感染引起的。因此，RV 感染可能通过这些改变损害鼻上皮的黏液纤毛转运。
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