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Cigarette smoke condensate inhibits ENaC -subunit expression in lung epithelial cells

¹ McGuire VA Medical Center, Depts of ² Medicine, and ³ Physiology, Virginia Commonwealth University, Richmond, VA, USA.

CORRESPONDENCE: S. Chu, McGuire VA Medical Center (151), 1201 Broad Rock Blv., Richmond, VA 23249, USA. Fax: 1 8046755359. E-mail: schu{at}hsc.vcu.edu

Keywords: Ion channel, steroid, tobacco, transcription

Received: February 5, 2007
Accepted May 9, 2007

Cigarette smoke has been associated with lung fluid accumulation and increased risk of acute respiratory distress syndrome. It was postulated that ENaC -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 -subunit expression was measured using immunoblotting, quantitative PCR and promoter–reporter assays.

The current authors found that CSC, without affecting cell survival, suppressed -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 -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 -subunit expression. This inhibition of dexamethasone was partially reversed by withdrawal of CSC.

The present results demonstrate that cigarette smoke condensate inhibits ENaC -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 -subunit expression in smokers’ lungs compared with nonsmokers’ lungs, and that quitting smoking might improve the effectiveness of dexamethasone.

This article has been cited by other articles:

				H. Xu and S. Chu ENaC {alpha}-subunit variants are expressed in lung epithelial cells and are suppressed by oxidative stress Am J Physiol Lung Cell Mol Physiol, December 1, 2007; 293(6): L1454 - L1462. [Abstract] [Full Text] [PDF]