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Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema

Chronic bronchitis and emphysema are pathologic features of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS)-induced endoplasmic reticulum (ER) stress has been implicated in the COPD development, but the molecular mechanism by which it contributes to COPD etiology and the specific...

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Autores principales: Wang, Yong, Wu, Zhen-Zhen, Wang, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652808/
https://www.ncbi.nlm.nih.gov/pubmed/29100417
http://dx.doi.org/10.18632/oncotarget.20768
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author Wang, Yong
Wu, Zhen-Zhen
Wang, Wei
author_facet Wang, Yong
Wu, Zhen-Zhen
Wang, Wei
author_sort Wang, Yong
collection PubMed
description Chronic bronchitis and emphysema are pathologic features of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS)-induced endoplasmic reticulum (ER) stress has been implicated in the COPD development, but the molecular mechanism by which it contributes to COPD etiology and the specific role it plays in COPD pathogenesis remain poorly understood. Here, we aimed to determine the role of ER stress in the pathogenesis of CS-induced airway inflammation and emphysema. Exposure to CS significantly increased the expression of ER stress markers in Beas-2B cells and in mouse lungs, possibly through the production of oxidative stress. Further, inhibition of ER stress by 4-phenylbutyric acid (4-PBA) reduced CS extract-induced inflammation in Beas-2B cells through the modulation of NF-κB signaling. 4-PBA also protected against CS-induced airway inflammation and the development of emphysema in mice, which was associated with a reduction in NF-κB activation and alveolar cell apoptosis in the lungs. Taken together, our results suggest that ER stress is crucial for CS-induced inflammation and emphysema, and that targeting ER stress may represent a novel approach to the treatment of COPD.
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spelling pubmed-56528082017-11-02 Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema Wang, Yong Wu, Zhen-Zhen Wang, Wei Oncotarget Research Paper Chronic bronchitis and emphysema are pathologic features of chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS)-induced endoplasmic reticulum (ER) stress has been implicated in the COPD development, but the molecular mechanism by which it contributes to COPD etiology and the specific role it plays in COPD pathogenesis remain poorly understood. Here, we aimed to determine the role of ER stress in the pathogenesis of CS-induced airway inflammation and emphysema. Exposure to CS significantly increased the expression of ER stress markers in Beas-2B cells and in mouse lungs, possibly through the production of oxidative stress. Further, inhibition of ER stress by 4-phenylbutyric acid (4-PBA) reduced CS extract-induced inflammation in Beas-2B cells through the modulation of NF-κB signaling. 4-PBA also protected against CS-induced airway inflammation and the development of emphysema in mice, which was associated with a reduction in NF-κB activation and alveolar cell apoptosis in the lungs. Taken together, our results suggest that ER stress is crucial for CS-induced inflammation and emphysema, and that targeting ER stress may represent a novel approach to the treatment of COPD. Impact Journals LLC 2017-09-08 /pmc/articles/PMC5652808/ /pubmed/29100417 http://dx.doi.org/10.18632/oncotarget.20768 Text en Copyright: © 2017 Wang et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Wang, Yong
Wu, Zhen-Zhen
Wang, Wei
Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema
title Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema
title_full Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema
title_fullStr Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema
title_full_unstemmed Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema
title_short Inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema
title_sort inhibition of endoplasmic reticulum stress alleviates cigarette smoke-induced airway inflammation and emphysema
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5652808/
https://www.ncbi.nlm.nih.gov/pubmed/29100417
http://dx.doi.org/10.18632/oncotarget.20768
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