Anti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells.
AuthorsGreene, C M
Miller, S D W
Carroll, T P
Oglesby, I K
Taggart, C C
McElvaney, N G
O'Neill, S J
AffiliationDept of Medicine Respiratory Research Division, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland. firstname.lastname@example.org
In Situ Nick-End Labeling
Inhibitor of Apoptosis Proteins
Reverse Transcriptase Polymerase Chain Reaction
alpha 1-Antitrypsin Deficiency
bcl-Associated Death Protein
MetadataShow full item record
CitationAnti-apoptotic effects of Z alpha1-antitrypsin in human bronchial epithelial cells. 2010, 35 (5):1155-63 Eur. Respir. J.
JournalThe European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
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.
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