期刊
JOURNAL OF CELL BIOLOGY
卷 183, 期 3, 页码 429-439出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200801186
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资金
- National Institutes of Health [HL68111, ES09237]
- University of New Mexico General Clinical Research Center (National Institutes of Health National Center for Research Resources General Clinical Research Center) [5MO1 RR099]
FN gamma induces cell death in epithelial cells, but the mediator for this death pathway has not been identified. In this study, we find that expression of Bik/Blk/Nbk is increased in human airway epithelial cells (AECs [HAECs]) in response to IFN gamma. Expression of Bik but not mutant BikL61G induces and loss of Bik suppresses IFN gamma-induced cell death in HAECs. IFN gamma treatment and Bik expression increase cathepsin B and D messenger RNA levels and reduce levels of phospho-extracellular regulated kinase 1/2(ERK1/2) in the nuclei of bik(+/+) compared with bik(-/-) murine AECs. Bik but not BikL61G interacts with and suppresses nuclear translocation of phospho-ERK1/2, and suppression of ERK1/2 activation inhibits IFN gamma- and Bik-induced cell death. Furthermore, after prolonged exposure to allergen, hyperplastic epithelial cells persist longer, and nuclear phospho-ERK is more prevalent in airways of IFN gamma(-/-) or bik(-/-) compared with wild-type mice. These results demonstrate that IFN gamma requires Bik to suppress nuclear localization of phospho-ERK1/2 to channel cell death in AECs.
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