PT  - JOURNAL ARTICLE
AU  - C. M. Greene
AU  - S. D. W. Miller
AU  - T. P. Carroll
AU  - I. K. Oglesby
AU  - F. Ahmed
AU  - M. O'Mahony
AU  - C. C. Taggart
AU  - N. G. McElvaney
AU  - S. J. O'Neill
TI  - Anti-apoptotic effects of Z α<sub>1</sub>-antitrypsin in human bronchial
epithelial cells
AID  - 10.1183/09031936.00191908
DP  - 2010 May 01
TA  - European Respiratory Journal
PG  - 1155--1163
VI  - 35
IP  - 5
4099  - http://erj.ersjournals.com/content/35/5/1155.short
4100  - http://erj.ersjournals.com/content/35/5/1155.full
SO  - Eur Respir J2010 May 01; 35
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.