Bombesin Receptor-Activated Protein (BRAP) Modulates NF-kappa B Activation in Bronchial Epithelial Cells by Enhancing HDAC Activity

摘要

Our previous studies provided evidence that bombesin receptor-activated protein (BRAP), encoded by C6ORF89, is widely expressed in human airway epithelial cells and may play a role in the stress response of lung epithelia. In this study, we demonstrated that BRAP has a regulatory effect on NF-kappa B transcriptional activity in cultured human bronchial epithelial cells (HBECs). BRAP overexpression by gene transfer inhibited both basal and inducible NF-kappa B transcriptional activity in HBECs, whereas BRAP knockdown had the opposite effect. BRAP was shown to regulate NF-kappa B activity by enhancing histone deacetylase (HDAC) activity. In addition, BRAP might increase HDAC activity that leads to NF-kappa B activation via its putative C-terminal domain. Our study suggests that the BRAP protein is an important regulator of immune and inflammatory responses in the human airway epithelium. (C) 2015 Wiley Periodicals, Inc.