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This Article Full Text Full Text (PDF) All Versions of this Article: 293/5/L1339    most recent 00121.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Cheng, G. Articles by Agrawal, D. K. Search for Related Content PubMed PubMed Citation Articles by Cheng, G. Articles by Agrawal, D. K.

Involvement of chloride channels in TGF-1-induced apoptosis of human bronchial epithelial cells

Departments of ¹Biomedical Sciences, ²Internal Medicine, and ³Medical Microbiology and Immunology, Creighton University School of Medicine, Omaha, Nebraska

Submitted 27 March 2007 ; accepted in final form 11 September 2007

Widespread damage of airway epithelium and defective epithelial repair are hallmarks of chronic asthma. Growth factors and cytokines spatially and temporally regulate epithelial shedding and repair. Within this context, a key function is exerted by transforming growth factor (TGF)-. Recent growing evidence suggests that chloride (Cl^–) channels are critical to cell apoptosis. We examined the effects of TGF-1 on Cl^– channel expression and activity and its relationship with apoptosis in human bronchial epithelial cells (HBECs). The small interfering RNA (siRNA) approach was used to investigate the potential role of CLC-3, a member of the volume-regulated Cl^– channel family, in apoptosis of HBECs. TGF-1 significantly induced HBEC apoptosis, which paralleled to a significant decrease in the endogenous expression of CLC-3 protein and mRNA transcripts. Outward rectifying and voltage-dependent CLC-3-like Cl^– currents in HBECs were diminished by TGF-1. siRNA for CLC-3 abolished Cl^– current and enhanced TGF-1-induced cell apoptosis. Overexpression of CLC-3 in HBECs inhibited TGF-1-induced cell apoptosis. Bcl-2 was also downregulated after TGF- stimulation. TGF-1-induced cell apoptosis was suppressed in Bcl-2-transfected HBECs. Our data demonstrate that CLC-3-like voltage-gated chloride channels play a critical role in TGF--induced apoptosis of human airway epithelial cells.

airway epithelial cells; Bcl-2; chronic asthma