Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers
Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers
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DOI：
10.1164/rccm.200508-1330oc
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发表时间：
2006-05-15
影响因子：
24.7
通讯作者：
Durie, Peter
中科院分区：
文献类型：
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作者：
Cantin, Andre M.;Hanrahan, John W.;Durie, Peter
理由：香烟烟雾提取物抑制人支气管上皮细胞的氯化物分泌。氧化剂降低囊性纤维化跨膜传导调节因子（CFTR）的基因表达、蛋白表达和功能。目的：由于香烟烟雾是氧化剂的丰富来源，我们验证了CFTR可能在体内和体外暴露于香烟烟雾中受到抑制的假设。方法：观察香烟烟雾暴露对Calu-3和T84细胞CFTR表达及功能的影响。还研究了26名男性（9名吸烟者，17名非吸烟者）的鼻电位差异（pd），这些男性在不育调查中没有检测到CFTR基因突变。CFTR的表达和功能通过Northern blotting、Western blotting和camp依赖性I-125外排法测定。对每个受试者进行了广泛的CFTR基因分型。在基线和阿米洛利、无氯缓冲液和异丙肾上腺素灌注期间进行鼻腔PD测量。主要结果：吸烟降低了Calu-3和T84细胞系CFTR的表达和功能。此外，与不吸烟者相比，吸烟者的鼻部pd表现出典型的CFTR缺乏模式，对无氯化物缓冲液和异丙肾上腺素的反应迟钝（-9.6 +/- 4.0 vs -22.3 +/- 10.1 mV; p < 0.001）。结论：在体外实验中，吸烟降低了CFTR基因、蛋白和功能的表达，获得性CFTR缺乏发生在吸烟者的鼻呼吸道上皮中。我们认为获得性CFTR缺乏可能与慢性支气管炎等卷烟引起的疾病的生理病理有关。
Rationale: Cigarette smoke extract inhibits chloride secretion in human bronchial epithelial cells. Oxidants decrease gene expression, protein expression, and function of the cystic fibrosis transmembrane conductance regulator (CFTR).Objectives: Because cigarette smoke is a rich source of oxidants, we verified the hypothesis that CFTR may be suppressed by exposure to cigarette smoke in vitro and in vivo.Methods: The effects of cigarette smoke exposure on Calu-3 and T84 cell CFTR expression and function were observed. Also studied were the nasal potential differences (PDs) in 26 men (9 smokers, 17 nonsmokers) who had no detectable CFTR gene mutations as determined during investigations for infertility. CFTR expression and function were determined by Northern blotting, Western blotting, and cAMP-dependent I-125 efflux assays. Extensive CFTR genotyping was performed in each subject. Nasal PD measurements were made at baseline and during amiloride, chloride-free buffer, and isoproterenol perfusions.Main Results: Cigarette smoke decreased CFTR expression and function in Calu-3 and T84 cell lines. Furthermore, the nasal PDs of cigarette smokers showed a pattern typical of CFTR deficiency with a blunted response to chloride-free buffer and isoproterenol compared with nonsmokers (-9.6 +/- 4.0 vs. -22.3 +/- 10.1 mV; p < 0.001).Conclusions: We conclude that cigarette smoke decreases the expression of CFTR gene, protein, and function in vitro and that acquired CFTR deficiency occurs in the nasal respiratory epithelium of cigarette smokers. We suggest that acquired CFTR deficiency may contribute to the physiopathology of cigarette-induced diseases such as chronic bronchitis.