Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice

Abstract Acute lung injury (ALI) is the result of damage to the capillary endothelia and the alveolar epithelial cell caused by various direct and indirect factors, leading to significant pulmonary interstitial and alveolar edema and acute hypoxic respiratory insufficiency. A subset of ALI cases pro...

Full description

Saved in:
Bibliographic Details
Main Authors: Tongtong Xue, Qianyi Zhang, Tiantian Zhang, Lingxin Meng, Jing Liu, Dan Chai, Yuming Liu, Zhongyi Yang, Ran Jiao, Yunyao Cui, Jingjing Gao, Xiaohe Li, Aiguo Xu, Honggang Zhou
Format: Article
Language:English
Published: BMC 2024-09-01
Series:BMC Pulmonary Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12890-024-03273-6
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849737845321760768
author Tongtong Xue
Qianyi Zhang
Tiantian Zhang
Lingxin Meng
Jing Liu
Dan Chai
Yuming Liu
Zhongyi Yang
Ran Jiao
Yunyao Cui
Jingjing Gao
Xiaohe Li
Aiguo Xu
Honggang Zhou
author_facet Tongtong Xue
Qianyi Zhang
Tiantian Zhang
Lingxin Meng
Jing Liu
Dan Chai
Yuming Liu
Zhongyi Yang
Ran Jiao
Yunyao Cui
Jingjing Gao
Xiaohe Li
Aiguo Xu
Honggang Zhou
author_sort Tongtong Xue
collection DOAJ
description Abstract Acute lung injury (ALI) is the result of damage to the capillary endothelia and the alveolar epithelial cell caused by various direct and indirect factors, leading to significant pulmonary interstitial and alveolar edema and acute hypoxic respiratory insufficiency. A subset of ALI cases progresses to irreversible pulmonary fibrosis, a condition with fatal implications. Zafirlukast is a leukotriene receptor antagonist licensed for asthma prevention and long-term treatment. This study demonstrated a significant improvement in lung tissue pathology and a reduction in inflammatory cell infiltration in models of lipopolysaccharide (LPS)-induced ALI and bleomycin (BLM)-induced lung inflammation following zafirlukast administration, both in vivo and in vitro. Moreover, zafirlukast was found to suppress the inflammatory response of alveolar epithelial cells in vitro and lung inflammation in vivo by reducing the activation of the TLR4/NF-κB/NLRP3 inflammasome pathway. In conclusion, zafirlukast relieved lung injury and the infiltration of inflammatory cells in the lung by regulating the TLR4/NF-κB/NLRP3 pathway.
format Article
id doaj-art-9086ce84774b4ff080b8ab6f44bcddc4
institution DOAJ
issn 1471-2466
language English
publishDate 2024-09-01
publisher BMC
record_format Article
series BMC Pulmonary Medicine
spelling doaj-art-9086ce84774b4ff080b8ab6f44bcddc42025-08-20T03:06:48ZengBMCBMC Pulmonary Medicine1471-24662024-09-0124111510.1186/s12890-024-03273-6Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in miceTongtong Xue0Qianyi Zhang1Tiantian Zhang2Lingxin Meng3Jing Liu4Dan Chai5Yuming Liu6Zhongyi Yang7Ran Jiao8Yunyao Cui9Jingjing Gao10Xiaohe Li11Aiguo Xu12Honggang Zhou13Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical UniversityState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityTianjin Jikun Technology Co., LtdTianjin Jikun Technology Co., LtdState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityDepartment of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Zhengzhou UniversityState Key Laboratory of Medicinal Chemical Biology, College of Pharmacy, College of Life Sciences, Nankai UniversityAbstract Acute lung injury (ALI) is the result of damage to the capillary endothelia and the alveolar epithelial cell caused by various direct and indirect factors, leading to significant pulmonary interstitial and alveolar edema and acute hypoxic respiratory insufficiency. A subset of ALI cases progresses to irreversible pulmonary fibrosis, a condition with fatal implications. Zafirlukast is a leukotriene receptor antagonist licensed for asthma prevention and long-term treatment. This study demonstrated a significant improvement in lung tissue pathology and a reduction in inflammatory cell infiltration in models of lipopolysaccharide (LPS)-induced ALI and bleomycin (BLM)-induced lung inflammation following zafirlukast administration, both in vivo and in vitro. Moreover, zafirlukast was found to suppress the inflammatory response of alveolar epithelial cells in vitro and lung inflammation in vivo by reducing the activation of the TLR4/NF-κB/NLRP3 inflammasome pathway. In conclusion, zafirlukast relieved lung injury and the infiltration of inflammatory cells in the lung by regulating the TLR4/NF-κB/NLRP3 pathway.https://doi.org/10.1186/s12890-024-03273-6ZafirlukastAcute lung injuryEpithelial cellNF-κB
spellingShingle Tongtong Xue
Qianyi Zhang
Tiantian Zhang
Lingxin Meng
Jing Liu
Dan Chai
Yuming Liu
Zhongyi Yang
Ran Jiao
Yunyao Cui
Jingjing Gao
Xiaohe Li
Aiguo Xu
Honggang Zhou
Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice
BMC Pulmonary Medicine
Zafirlukast
Acute lung injury
Epithelial cell
NF-κB
title Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice
title_full Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice
title_fullStr Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice
title_full_unstemmed Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice
title_short Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice
title_sort zafirlukast ameliorates lipopolysaccharide and bleomycin induced lung inflammation in mice
topic Zafirlukast
Acute lung injury
Epithelial cell
NF-κB
url https://doi.org/10.1186/s12890-024-03273-6
work_keys_str_mv AT tongtongxue zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT qianyizhang zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT tiantianzhang zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT lingxinmeng zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT jingliu zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT danchai zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT yumingliu zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT zhongyiyang zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT ranjiao zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT yunyaocui zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT jingjinggao zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT xiaoheli zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT aiguoxu zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice
AT honggangzhou zafirlukastameliorateslipopolysaccharideandbleomycininducedlunginflammationinmice