Cystic Fibrosis Transmembrane Conductance Regulator Function Is Suppressed in Cigarette Smokers

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). Because cigarette smoke is a rich source of oxidants, we verified the hypoth...

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Bibliographic Details
Published in:American journal of respiratory and critical care medicine 2006-05, Vol.173 (10), p.1139-1144
Main Authors: Cantin, Andre M, Hanrahan, John W, Bilodeau, Ginette, Ellis, Lynda, Dupuis, Annie, Liao, Jie, Zielenski, Julian, Durie, Peter
Format: Article
Language:English
Subjects:
Adult
Analysis of Variance
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Biological and medical sciences
Blotting, Northern
Blotting, Western
Case-Control Studies
Cells, Cultured
Chlorides - metabolism
Cystic Fibrosis - blood
Cystic Fibrosis - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - genetics
Cystic Fibrosis Transmembrane Conductance Regulator - metabolism
Down-Regulation
Epithelial Cells - cytology
Gene Expression Regulation
Genetic Predisposition to Disease
Genotype
Glutathione - metabolism
History, Medieval
Humans
Intensive care medicine
Male
Medical sciences
Nasal Mucosa - cytology
Pneumology
Polymerase Chain Reaction
Probability
Reference Values
Respiratory system : syndromes and miscellaneous diseases
RNA, Messenger - analysis
Sensitivity and Specificity
Smoking - genetics
Smoking - metabolism
Tobacco, tobacco smoking
Toxicology
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Summary: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). 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. 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 125I 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. 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). 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.
ISSN:1073-449X
1535-4970
DOI:10.1164/rccm.200508-1330OC