RT Journal Article SR Electronic T1 Anti-apoptotic effects of Z α1-antitrypsin in human bronchial epithelial cells JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 1155 OP 1163 DO 10.1183/09031936.00191908 VO 35 IS 5 A1 C. M. Greene A1 S. D. W. Miller A1 T. P. Carroll A1 I. K. Oglesby A1 F. Ahmed A1 M. O'Mahony A1 C. C. Taggart A1 N. G. McElvaney A1 S. J. O'Neill YR 2010 UL http://erj.ersjournals.com/content/35/5/1155.abstract AB 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.