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

J Cell Biochem. 2016 May;117(5):1069-77. doi: 10.1002/jcb.25406. Epub 2015 Oct 18.

Abstract

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-κB transcriptional activity in cultured human bronchial epithelial cells (HBECs). BRAP overexpression by gene transfer inhibited both basal and inducible NF-κB transcriptional activity in HBECs, whereas BRAP knockdown had the opposite effect. BRAP was shown to regulate NF-κB activity by enhancing histone deacetylase (HDAC) activity. In addition, BRAP might increase HDAC activity that leads to NF-κB 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.

Keywords: BOMBESIN RECEPTOR-ACTIVATED PROTEIN; BRONCHIAL EPITHELIAL CELLS; HISTONE DEACETYLASE; NF-κB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Bronchi / cytology
  • Cell Line
  • Epithelial Cells / metabolism*
  • HEK293 Cells
  • Histone Deacetylase 1 / metabolism*
  • Histone Deacetylase 2 / metabolism*
  • Humans
  • Interleukin-8 / metabolism
  • Lung / drug effects
  • Lung / metabolism
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • NF-kappa B / metabolism*
  • Oxidants, Photochemical / pharmacology
  • Ozone / pharmacology
  • RNA Interference
  • Reactive Oxygen Species / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*

Substances

  • Interleukin-8
  • NF-kappa B
  • Oxidants, Photochemical
  • Reactive Oxygen Species
  • Ozone
  • BRAP protein, human
  • Ubiquitin-Protein Ligases
  • Histone Deacetylase 1
  • Histone Deacetylase 2