TY - JOUR T1 - Cigarette smoke condensate inhibits ENaC α-subunit expression in lung epithelial cells JF - European Respiratory Journal JO - Eur Respir J SP - 633 LP - 642 DO - 10.1183/09031936.00014107 VL - 30 IS - 4 AU - H. Xu AU - T. J. Ferro AU - S. Chu Y1 - 2007/10/01 UR - http://erj.ersjournals.com/content/30/4/633.abstract N2 - Cigarette smoke has been associated with lung fluid accumulation and increased risk of acute respiratory distress syndrome. It was postulated that ENaC α-subunit, which plays a critical role in lung fluid absorption, is affected by cigarette smoke. Cigarette smoke condensate (CSC) was used to treat a human lung epithelial cell line. ENaC α-subunit expression was measured using immunoblotting, quantitative PCR and promoter–reporter assays. The current authors found that CSC, without affecting cell survival, suppressed α-subunit expression at the transcriptional level in a dose- and time-dependent fashion. This suppression is neither related to nicotine nor due to an increase of hydrogen peroxide levels in CSC-treated cells. CSC also suppressed α-subunit core promoter activity. Dexamethasone, which activates the core promoter, was able to attenuate the inhibitory effect of CSC. However, in the presence of CSC, dexamethasone was unable to elicit a full-scale activation of α-subunit expression. This inhibition of dexamethasone was partially reversed by withdrawal of CSC. The present results demonstrate that cigarette smoke condensate inhibits ENaC α-subunit expression at the transcriptional level through its promoter. This inhibition could be reversed by dexamethasone. The results also suggest that higher doses of dexamethasone may be needed to activate α-subunit expression in smokers’ lungs compared with nonsmokers’ lungs, and that quitting smoking might improve the effectiveness of dexamethasone. ER -