Show simple item record

dc.contributor.authorGreene, C M
dc.contributor.authorMiller, S D W
dc.contributor.authorCarroll, T P
dc.contributor.authorOglesby, I K
dc.contributor.authorAhmed, F
dc.contributor.authorO'Mahony, M
dc.contributor.authorTaggart, C C
dc.contributor.authorMcElvaney, N G
dc.contributor.authorO'Neill, S J
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
html.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.


This item appears in the following Collection(s)

Show simple item record