Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers

André M. Cantin*, John W. Hanrahan, Ginette Bilodeau, Lynda Ellis, Annie Dupuis, Jie Liao, Julian Zielenski, Peter Durie

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

190 Scopus citations

Abstract

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 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. 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.

Original languageEnglish (US)
Pages (from-to)1139-1144
Number of pages6
JournalAmerican journal of respiratory and critical care medicine
Volume173
Issue number10
DOIs
StatePublished - May 15 2006

Keywords

  • Antioxidants
  • Chloride channels
  • Cystic fibrosis
  • Epithelial cells
  • Oxidants
  • Reactive oxygen species

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

Fingerprint Dive into the research topics of 'Cystic fibrosis transmembrane conductance regulator function is suppressed in cigarette smokers'. Together they form a unique fingerprint.

Cite this