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

¹ McGuire VA Medical Center, Richmond, VA
² McGuire VA Medical Center, Richmond, VA; Dept of Medicine, Virginia Commonwealth University, Richmond, VA; and Dept of Physiology, Virginia Commonwealth University, Richmond, VA
³ McGuire VA Medical Center, Richmond, VA; and Dept of Physiology, Virginia Commonwealth University, Richmond, VA

^* To whom correspondence should be addressed. E-mail: schu{at}hsc.vcu.edu.

	Abstract

Cigarette smoke has been associated with lung fluid accumulation and increased risk of ARDS. We postulated that ENaC -subunit, which plays a critical role in lung fluid absorption, is affected by cigarette smoke.

We used cigarette smoke condensate (CSC) to treat a human lung epithelial cell line. ENaC -subunit expression was measured using immunoblotting, quantitative PCR, and promoter-reporter assays.

We 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 H₂O₂ in CSC-treated cells. CSC also suppressed -subunit core promoter activity. Dexamethasone, which activates the core promoter, was able to attenuate CSC's inhibitory effect. However, in the presence of CSC, dexamethasone was unable to elicit a full-scale activation of -subunit expression. This inhibition on dexamethasone was partially reversed by withdrawal of CSC.

Our results demonstrate that CSC inhibits ENaC -subunit expression at the transcriptional level through its promoter. This inhibition could be reversed by dexamethasone. Our results also suggest that higher doses of dexamethasone maybe needed to activate -subunit expression in smoker lungs compared to non-smoker lungs, and 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]