Anti-apoptotic effects of Z alpha-1 antitrypsin in human bronchial epithelial cells.

C.M. Green, S.D. Miller, T.P. Carroll, I.K. Oglesby, F. Ahmed, M. O'Mahony, Clifford Taggart, N.G. McElvaney, S.J. O'Neill

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25 Citations (Scopus)


α1-antitrypsin (α1-AT) deficiency is a genetic disease which manifests as early-onset emphysema or liver disease. Although the majority of α1-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 α1-AT (ZAAT) expression on apoptosis in a human bronchial epithelial cell line (16HBE14o-) and delineate the mechanisms involved.

Control, M variant α1-AT (MAAT)- or ZAAT-expressing cells were assessed for apoptosis, caspase-3 activity, cell viability, phosphorylation of Bad, nuclear factor (NF)-κB 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-κB-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-κB. 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.
Original languageEnglish
Pages (from-to)000-000
Number of pages1
JournalThe European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology
Issue number5
Publication statusPublished - May 2010

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine


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