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Title: Bombesin receptor-activated protein regulates neutrophil elastase-induced mucin5AC hypersecretion in human bronchial epithelial cells

Abstract

Bombesin receptor-activated protein (BRAP) is highly expressed in human bronchial epithelial cells. Recent studies have shown that BRAP reduces oxidative stress, inhibits airway inflammation and suppresses nuclear factor kappaB (NF-κB) activity. Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases. Neutrophil elastase (NE) is a potent inducer of mucin5AC (MUC5AC), which is considered the predominant mucin secreted by human airway epithelial cells. Here, we hypothesize that BRAP may regulate NE-induced MUC5AC hypersecretion in a bronchial epithelial cell line (HBE16). We also investigated the underlying mechanism involved in the process. In this study, we found that BRAP was present in HBE16 human bronchial epithelial cells and was significantly increased by NE. Next, we found that the up-regulation of BRAP by pEGFP-N1-BRAP caused a significant decrease in the increased levels of MUC5AC expression, NF-κB activity, and the phosphorylation of extracellular signal-regulated kinases (ERK) and epidermal growth factor receptor (EGFR) induced by NE. Meanwhile, there was a significant decrease in ROS, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels when BRAP was up-regulated by pEGFP-N1-BRAP. Moreover, when cells were transfected with pEGFP-N1-BRAP and pretreated with NF-κB, ERK or EGFR inhibitors before the NE stimulation, there were further decreased inmore » MUC5AC expression, NF-κB activity, and the phosphorylation of ERK and EGFR. These results suggest that BRAP plays an important role in airway inflammation and its overexpression may regulate NE-induced MUC5AC hypersecretion in HBE16 cells via the EGFR/ERK/NF-κB signaling pathway. - Highlights: • BRAP is highly expressed in HBE16 cell and NE can induce BRAP expression. • BRAP up-regulation reduces MUC5AC expression, NF-κB activity, p-ERK and p-EGFR. • BRAP overexpression can decrease ROS production, IL-1β and IL-6 expression. • BRAP regulate NE-induced MUC5AC hypersecretion via EGFR/ERK/NF-κB pathway.« less

Authors:
 [1];  [1];  [2];  [1];  [3];  [1];  [4]
  1. Division of Respiratory Medicine, Second Affiliated Hospital, Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing 400010 (China)
  2. Department of Respiratory and Geriatrics Medicine, Chongqing Public Health Medical Center, No. 2, Huangjiaowan Road, Xiaolongkan Street, Shapingba District, Chongqing 400010 (China)
  3. Department of Respiratory Medicine, First Affiliated Hospital, Hainan Medical University, No. 31, Longhua Road, Haikou 570102, Hainan (China)
  4. (China)
Publication Date:
OSTI Identifier:
22738142
Resource Type:
Journal Article
Journal Name:
Experimental Cell Research
Additional Journal Information:
Journal Volume: 357; Journal Issue: 2; Other Information: Copyright (c) 2017 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0014-4827
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; BRONCHI; GENE REGULATION; INFLAMMATION; NEUTROPHILS; REGULATIONS

Citation Formats

Xu, Qing, Chen, Ling-Xiu, Ran, Dan-Hua, Xie, Wen-Yue, Li, Qi, Zhou, Xiang-Dong, and Department of Respiratory Medicine, First Affiliated Hospital, Hainan Medical University, No. 31, Longhua Road, Haikou 570102, Hainan. Bombesin receptor-activated protein regulates neutrophil elastase-induced mucin5AC hypersecretion in human bronchial epithelial cells. United States: N. p., 2017. Web. doi:10.1016/J.YEXCR.2017.05.002.
Xu, Qing, Chen, Ling-Xiu, Ran, Dan-Hua, Xie, Wen-Yue, Li, Qi, Zhou, Xiang-Dong, & Department of Respiratory Medicine, First Affiliated Hospital, Hainan Medical University, No. 31, Longhua Road, Haikou 570102, Hainan. Bombesin receptor-activated protein regulates neutrophil elastase-induced mucin5AC hypersecretion in human bronchial epithelial cells. United States. doi:10.1016/J.YEXCR.2017.05.002.
Xu, Qing, Chen, Ling-Xiu, Ran, Dan-Hua, Xie, Wen-Yue, Li, Qi, Zhou, Xiang-Dong, and Department of Respiratory Medicine, First Affiliated Hospital, Hainan Medical University, No. 31, Longhua Road, Haikou 570102, Hainan. Tue . "Bombesin receptor-activated protein regulates neutrophil elastase-induced mucin5AC hypersecretion in human bronchial epithelial cells". United States. doi:10.1016/J.YEXCR.2017.05.002.
@article{osti_22738142,
title = {Bombesin receptor-activated protein regulates neutrophil elastase-induced mucin5AC hypersecretion in human bronchial epithelial cells},
author = {Xu, Qing and Chen, Ling-Xiu and Ran, Dan-Hua and Xie, Wen-Yue and Li, Qi and Zhou, Xiang-Dong and Department of Respiratory Medicine, First Affiliated Hospital, Hainan Medical University, No. 31, Longhua Road, Haikou 570102, Hainan},
abstractNote = {Bombesin receptor-activated protein (BRAP) is highly expressed in human bronchial epithelial cells. Recent studies have shown that BRAP reduces oxidative stress, inhibits airway inflammation and suppresses nuclear factor kappaB (NF-κB) activity. Mucus overproduction is an important feature in patients with chronic inflammatory airway diseases. Neutrophil elastase (NE) is a potent inducer of mucin5AC (MUC5AC), which is considered the predominant mucin secreted by human airway epithelial cells. Here, we hypothesize that BRAP may regulate NE-induced MUC5AC hypersecretion in a bronchial epithelial cell line (HBE16). We also investigated the underlying mechanism involved in the process. In this study, we found that BRAP was present in HBE16 human bronchial epithelial cells and was significantly increased by NE. Next, we found that the up-regulation of BRAP by pEGFP-N1-BRAP caused a significant decrease in the increased levels of MUC5AC expression, NF-κB activity, and the phosphorylation of extracellular signal-regulated kinases (ERK) and epidermal growth factor receptor (EGFR) induced by NE. Meanwhile, there was a significant decrease in ROS, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels when BRAP was up-regulated by pEGFP-N1-BRAP. Moreover, when cells were transfected with pEGFP-N1-BRAP and pretreated with NF-κB, ERK or EGFR inhibitors before the NE stimulation, there were further decreased in MUC5AC expression, NF-κB activity, and the phosphorylation of ERK and EGFR. These results suggest that BRAP plays an important role in airway inflammation and its overexpression may regulate NE-induced MUC5AC hypersecretion in HBE16 cells via the EGFR/ERK/NF-κB signaling pathway. - Highlights: • BRAP is highly expressed in HBE16 cell and NE can induce BRAP expression. • BRAP up-regulation reduces MUC5AC expression, NF-κB activity, p-ERK and p-EGFR. • BRAP overexpression can decrease ROS production, IL-1β and IL-6 expression. • BRAP regulate NE-induced MUC5AC hypersecretion via EGFR/ERK/NF-κB pathway.},
doi = {10.1016/J.YEXCR.2017.05.002},
journal = {Experimental Cell Research},
issn = {0014-4827},
number = 2,
volume = 357,
place = {United States},
year = {2017},
month = {8}
}