Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.

Hdl Handle:
http://hdl.handle.net/10147/127265
Title:
Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.
Authors:
Greene, C M; Miller, S D W; Carroll, T P; Oglesby, I K; Ahmed, F; O'Mahony, M; Taggart, C C; McElvaney, N G; O'Neill, S J
Affiliation:
Dept of Medicine Respiratory Research Division, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. cmgreene@rcsi.ie
Citation:
Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells. 2010, 35 (5):1155-63 Eur. Respir. J.
Journal:
The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
Issue Date:
May-2010
URI:
http://hdl.handle.net/10147/127265
DOI:
10.1183/09031936.00191908
PubMed ID:
19840955
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.
Item Type:
Article
Language:
en
MeSH:
Adult; Apoptosis; Biopsy; Blotting, Western; Caspase 3; Cell Line; Cell Proliferation; Emphysema; Epithelial Cells; Female; Gene Expression; Humans; Immunoenzyme Techniques; In Situ Nick-End Labeling; Inhibitor of Apoptosis Proteins; Male; NF-kappa B; Phosphorylation; Respiratory Mucosa; Reverse Transcriptase Polymerase Chain Reaction; Up-Regulation; alpha 1-Antitrypsin; alpha 1-Antitrypsin Deficiency; bcl-Associated Death Protein
ISSN:
1399-3003

Full metadata record

DC FieldValue Language
dc.contributor.authorGreene, C Men
dc.contributor.authorMiller, S D Wen
dc.contributor.authorCarroll, T Pen
dc.contributor.authorOglesby, I Ken
dc.contributor.authorAhmed, Fen
dc.contributor.authorO'Mahony, Men
dc.contributor.authorTaggart, C Cen
dc.contributor.authorMcElvaney, N Gen
dc.contributor.authorO'Neill, S Jen
dc.date.accessioned2011-04-05T15:19:59Z-
dc.date.available2011-04-05T15:19:59Z-
dc.date.issued2010-05-
dc.identifier.citationAnti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells. 2010, 35 (5):1155-63 Eur. Respir. J.en
dc.identifier.issn1399-3003-
dc.identifier.pmid19840955-
dc.identifier.doi10.1183/09031936.00191908-
dc.identifier.urihttp://hdl.handle.net/10147/127265-
dc.description.abstractalpha(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.isoenen
dc.subject.meshAdult-
dc.subject.meshApoptosis-
dc.subject.meshBiopsy-
dc.subject.meshBlotting, Western-
dc.subject.meshCaspase 3-
dc.subject.meshCell Line-
dc.subject.meshCell Proliferation-
dc.subject.meshEmphysema-
dc.subject.meshEpithelial Cells-
dc.subject.meshFemale-
dc.subject.meshGene Expression-
dc.subject.meshHumans-
dc.subject.meshImmunoenzyme Techniques-
dc.subject.meshIn Situ Nick-End Labeling-
dc.subject.meshInhibitor of Apoptosis Proteins-
dc.subject.meshMale-
dc.subject.meshNF-kappa B-
dc.subject.meshPhosphorylation-
dc.subject.meshRespiratory Mucosa-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.subject.meshUp-Regulation-
dc.subject.meshalpha 1-Antitrypsin-
dc.subject.meshalpha 1-Antitrypsin Deficiency-
dc.subject.meshbcl-Associated Death Protein-
dc.titleAnti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.en
dc.typeArticleen
dc.contributor.departmentDept of Medicine Respiratory Research Division, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. cmgreene@rcsi.ieen
dc.identifier.journalThe European respiratory journal : official journal of the European Society for Clinical Respiratory Physiologyen
dc.description.provinceLeinster-

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