Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.
dc.contributor.author | Greene, C M | |
dc.contributor.author | Miller, S D W | |
dc.contributor.author | Carroll, T P | |
dc.contributor.author | Oglesby, I K | |
dc.contributor.author | Ahmed, F | |
dc.contributor.author | O'Mahony, M | |
dc.contributor.author | Taggart, C C | |
dc.contributor.author | McElvaney, N G | |
dc.contributor.author | O'Neill, S J | |
dc.date.accessioned | 2011-04-05T15:19:59Z | |
dc.date.available | 2011-04-05T15:19:59Z | |
dc.date.issued | 2010-05 | |
dc.identifier.citation | Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells. 2010, 35 (5):1155-63 Eur. Respir. J. | en |
dc.identifier.issn | 1399-3003 | |
dc.identifier.pmid | 19840955 | |
dc.identifier.doi | 10.1183/09031936.00191908 | |
dc.identifier.uri | http://hdl.handle.net/10147/127265 | |
dc.description.abstract | alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved. Control, M variant alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB activation and induced expression of a selection of pro- and anti-apoptotic genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival. | |
dc.language.iso | en | en |
dc.subject.mesh | Adult | |
dc.subject.mesh | Apoptosis | |
dc.subject.mesh | Biopsy | |
dc.subject.mesh | Blotting, Western | |
dc.subject.mesh | Caspase 3 | |
dc.subject.mesh | Cell Line | |
dc.subject.mesh | Cell Proliferation | |
dc.subject.mesh | Emphysema | |
dc.subject.mesh | Epithelial Cells | |
dc.subject.mesh | Female | |
dc.subject.mesh | Gene Expression | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Immunoenzyme Techniques | |
dc.subject.mesh | In Situ Nick-End Labeling | |
dc.subject.mesh | Inhibitor of Apoptosis Proteins | |
dc.subject.mesh | Male | |
dc.subject.mesh | NF-kappa B | |
dc.subject.mesh | Phosphorylation | |
dc.subject.mesh | Respiratory Mucosa | |
dc.subject.mesh | Reverse Transcriptase Polymerase Chain Reaction | |
dc.subject.mesh | Up-Regulation | |
dc.subject.mesh | alpha 1-Antitrypsin | |
dc.subject.mesh | alpha 1-Antitrypsin Deficiency | |
dc.subject.mesh | bcl-Associated Death Protein | |
dc.title | Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells. | en |
dc.type | Article | en |
dc.contributor.department | Dept of Medicine Respiratory Research Division, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. cmgreene@rcsi.ie | en |
dc.identifier.journal | The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology | en |
dc.description.province | Leinster | |
html.description.abstract | alpha(1)-antitrypsin (alpha(1)-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of alpha(1)-AT is produced by the liver, it is also produced by bronchial epithelial cells, amongst others, in the lung. Herein, we investigate the effects of mutant Z alpha(1)-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved. Control, M variant alpha(1)-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-kappaB activation and induced expression of a selection of pro- and anti-apoptotic genes. Expression of ZAAT in 16HBE14o- cells, like MAAT, inhibited basal and agonist-induced apoptosis. ZAAT expression also inhibited caspase-3 activity by 57% compared with control cells (p = 0.05) and was a more potent inhibitor than MAAT. Whilst ZAAT had no effect on the activity of Bad, its expression activated NF-kappaB-dependent gene expression above control or MAAT-expressing cells. In 16HBE14o- cells but not HEK293 cells, ZAAT upregulated expression of cIAP-1, an upstream regulator of NF-kappaB. cIAP1 expression was increased in ZAAT versus MAAT bronchial biopsies. The data suggest a novel mechanism by which ZAAT may promote human bronchial epithelial cell survival. |