Zafirlukast ameliorates lipopolysaccharide and bleomycin-induced lung inflammation in mice

IF 2.6 3区医学 Q2 RESPIRATORY SYSTEM

BMC Pulmonary Medicine Pub Date : 2024-09-16 DOI:10.1186/s12890-024-03273-6

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

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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.

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扎非司特可改善脂多糖和博莱霉素诱发的小鼠肺部炎症

急性肺损伤（ALI）是毛细血管内皮和肺泡上皮细胞受到各种直接或间接因素损伤的结果，导致肺间质和肺泡明显水肿以及急性缺氧性呼吸功能不全。部分 ALI 病例会发展为不可逆转的肺纤维化，这种情况具有致命影响。扎非鲁司特是一种白三烯受体拮抗剂，获准用于哮喘的预防和长期治疗。这项研究表明，在体内和体外服用扎非司特之后，脂多糖（LPS）诱导的 ALI 模型和博莱霉素（BLM）诱导的肺部炎症模型中的肺组织病理学状况得到了明显改善，炎症细胞浸润也有所减少。此外，研究还发现扎非司特通过减少 TLR4/NF-κB/NLRP3 炎性体通路的激活，抑制了体外肺泡上皮细胞的炎症反应和体内的肺部炎症。总之，扎非司特通过调节 TLR4/NF-κB/NLRP3 通路缓解了肺损伤和肺部炎症细胞的浸润。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

BMC Pulmonary Medicine RESPIRATORY SYSTEM-

CiteScore

4.40

自引率

3.20%

发文量

423

审稿时长

6-12 weeks

期刊介绍： BMC Pulmonary Medicine is an open access, peer-reviewed journal that considers articles on all aspects of the prevention, diagnosis and management of pulmonary and associated disorders, as well as related molecular genetics, pathophysiology, and epidemiology.