TY - T1的抗凋亡的影响Zα<子> 1-antitrypsin in human bronchial epithelial cells JF - European Respiratory Journal JO - Eur Respir J SP - 1155 LP - 1163 DO - 10.1183/09031936.00191908 VL - 35 IS - 5 AU - Greene, C. M. AU - Miller, S. D. W. AU - Carroll, T. P. AU - Oglesby, I. K. AU - Ahmed, F. AU - O'Mahony, M. AU - Taggart, C. C. AU - McElvaney, N. G. AU - O'Neill, S. J. Y1 - 2010/05/01 UR - //www.qdcxjkg.com/content/35/5/1155.abstract N2 - 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. ER -