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

Journal Article · Tue Aug 15 04:00:00 EDT 2017 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2017.05.002· OSTI ID:22738142

Xu, Qing ^[1]; Chen, Ling-Xiu ^[1]; Ran, Dan-Hua ^[2]; Xie, Wen-Yue ^[1]; Li, Qi ^[3]; Zhou, Xiang-Dong ^[1]

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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)

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.

• OSTI ID: 22738142
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 357; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
BRONCHI
GENE REGULATION
INFLAMMATION
NEUTROPHILS
REGULATIONS