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This Article Full Text Full Text (PDF) Supplemental Table All Versions of this Article: 294/6/L1102    most recent 00424.2007v1 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 PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Schwalm, K. Articles by Tesfaigzi, Y. Search for Related Content PubMed PubMed Citation Articles by Schwalm, K. Articles by Tesfaigzi, Y.

Expression of the proapoptotic protein Bax is reduced in bronchial mucous cells of asthmatic subjects

¹Lovelace Respiratory Research Institute, Albuquerque, New Mexico; ²Applied Biosystems, Foster City, California; ³University of New Mexico School of Medicine, General Clinical Research Center, Departments of Medicine and Biochemistry and Molecular Biology, Albuquerque, New Mexico; ⁴Department of Cell and Molecular Physiology, The University of North Carolina, Chapel Hill, North Carolina; and ⁵Respiratory Research Group, University of Calgary, Calgary, Alberta, Canada

Submitted 11 October 2007 ; accepted in final form 28 March 2008

The present studies were designed to determine whether our findings in mice showing that the Bcl-2-associated protein X (Bax), which plays a role in the resolution of allergen-induced mucous cell metaplasia, can be applied to asthma in humans. Immunostaining of autopsy tissues from mild and severe asthmatic subjects showed a significant reduction in the percentage of Bax-positive mucous cells compared with those from nonasthmatic controls. To exclude the possibility that postmortem changes may have affected Bax expression, Bax mRNA levels in airway epithelial cells obtained from nonsmoking asthmatic subjects were compared with those from nonasthmatic controls. Because the number of cells obtained by bronchial brushings is limited, we developed a robust preamplification procedure of cDNA before quantitative real-time PCR to allow detection of 100 gene targets from limited sample size, even when it was prepared from partially degraded RNA. cDNA was prepared by reverse transcription from RNA isolated from bronchial epithelial cells obtained by bronchial brushings from well-characterized subjects without lung disease and from subjects with mild asthma. Quantitative analysis showed that Bax mRNA levels were significantly reduced in samples obtained from asthma patients compared with nonasthma controls. Furthermore, Bax mRNA levels were reduced when primary airway epithelial cells from 10 individuals were treated in culture with the T helper 2 cytokine IL-13. These studies show that Bax expression is reduced in airway epithelial cells of even mild asthmatic subjects and suggest that restoring Bax expression may provide a clinical approach for restoring the normal numbers of epithelial cells and reduced mucous hypersecretion in asthma.

epithelial cell apoptosis; Bcl-2 family of proteins; lung airway epithelia; mucous cell hyperplasia; quantitative real-time polymerase chain reaction

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