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Title: Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma

Abstract

Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression ofmore » VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation of caveolin-1. • RXM inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. • Our findings expand our knowledge of the role of RXM in airway remodelling.« less

Authors:
 [1];  [2];  [2];  [2];  [2];  [2]
  1. Department of Radiology, Tianjin Hospital of Integrated Traditional Chinese and Western Medicine, Tianjin (China)
  2. Department of Respiration, Tianjin First Central Hospital, Tianjin (China)
Publication Date:
OSTI Identifier:
22649767
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 347; Journal Issue: 2; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ASTHMA; BLOOD; BLOOD VESSELS; CELL CYCLE; CELL PROLIFERATION; DOSES; GROWTH FACTORS; HUMAN POPULATIONS; INFLAMMATION; INHIBITION; MUSCLES; PATIENTS; PHOSPHOTRANSFERASES; PLANT GROWTH; RECEPTORS; REGULATIONS; SECRETION

Citation Formats

Pei, Qing-Mei, E-mail: 34713316@qq.com, Jiang, Ping, E-mail: jiangping@163.com, Yang, Min, E-mail: YangMin@163.com, Qian, Xue-Jiao, E-mail: qianxuejiao@163.com, Liu, Jiang-Bo, E-mail: LJB1984@163.com, and Kim, Sung-Ho, E-mail: chenghao0726@hotmail.com. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma. United States: N. p., 2016. Web. doi:10.1016/J.YEXCR.2016.08.024.
Pei, Qing-Mei, E-mail: 34713316@qq.com, Jiang, Ping, E-mail: jiangping@163.com, Yang, Min, E-mail: YangMin@163.com, Qian, Xue-Jiao, E-mail: qianxuejiao@163.com, Liu, Jiang-Bo, E-mail: LJB1984@163.com, & Kim, Sung-Ho, E-mail: chenghao0726@hotmail.com. Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma. United States. doi:10.1016/J.YEXCR.2016.08.024.
Pei, Qing-Mei, E-mail: 34713316@qq.com, Jiang, Ping, E-mail: jiangping@163.com, Yang, Min, E-mail: YangMin@163.com, Qian, Xue-Jiao, E-mail: qianxuejiao@163.com, Liu, Jiang-Bo, E-mail: LJB1984@163.com, and Kim, Sung-Ho, E-mail: chenghao0726@hotmail.com. Sat . "Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma". United States. doi:10.1016/J.YEXCR.2016.08.024.
@article{osti_22649767,
title = {Roxithromycin inhibits VEGF-induced human airway smooth muscle cell proliferation: Opportunities for the treatment of asthma},
author = {Pei, Qing-Mei, E-mail: 34713316@qq.com and Jiang, Ping, E-mail: jiangping@163.com and Yang, Min, E-mail: YangMin@163.com and Qian, Xue-Jiao, E-mail: qianxuejiao@163.com and Liu, Jiang-Bo, E-mail: LJB1984@163.com and Kim, Sung-Ho, E-mail: chenghao0726@hotmail.com},
abstractNote = {Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodelling, which is associated with increased airway smooth muscle (ASM) mass. Roxithromycin (RXM) has been widely used in asthma treatment; however, its mechanism of action is poorly understood. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodelling in patients with asthma, and shown to promote ASM cell proliferation. Here, we investigated the effect of RXM on VEGF-induced ASM cell proliferation and attempted to elucidate the underlying mechanisms of action. We tested the effect of RXM on proliferation and cell cycle progression, as well as on the expression of phospho-VEGF receptor 2 (VEGFR2), phospho-extracellular signal-regulated kinase 1/2 (ERK1/2), phospho-Akt, and caveolin-1 in VEGF-stimulated ASM cells. RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. Additionally, VEGF-induced ASM cell proliferation was suppressed by inhibiting the activity of ERK1/2, but not that of Akt. Furthermore, RXM treatment inhibits VEGF-induced activation of VEGFR2 and ERK and downregulation of caveolin-1 in a dose-dependent manner. RXM also inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. Collectively, our findings suggest that RXM inhibits VEGF-induced ASM cell proliferation by suppression of VEGFR2 and ERK1/2 activation and caveolin-1 down-regulation, which may be involved in airway remodelling. Further elucidation of the mechanisms underlying these observations should enable the development of treatments for smooth muscle hyperplasia-associated diseases of the airway such as asthma. - Highlights: • RXM inhibited VEGF-induced ASM cell proliferation and induced cell cycle arrest. • VEGF-induced cell proliferation was suppressed by inhibiting the activity of ERK1/2. • RXM inhibits activation of VEGFR2 and ERK and downregulation of caveolin-1. • RXM inhibited TGF-β-induced VEGF secretion by ASM cells and BEAS-2B cells. • Our findings expand our knowledge of the role of RXM in airway remodelling.},
doi = {10.1016/J.YEXCR.2016.08.024},
journal = {Experimental Cell Research},
number = 2,
volume = 347,
place = {United States},
year = {Sat Oct 01 00:00:00 EDT 2016},
month = {Sat Oct 01 00:00:00 EDT 2016}
}