Disulfiram alleviates acute lung injury and related intestinal mucosal barrier impairment by targeting GSDMD-dependent pyroptosis

被引:18
作者
Zhao, Jiping [1 ]
Wang, Hong [2 ]
Zhang, Jintao [3 ]
Ou, Fuwei [4 ]
Wang, Junfei [1 ]
Liu, Tian [1 ]
Wu, Jinxiang [1 ]
机构
[1] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Pulm & Crit Care Med, Jinan, Peoples R China
[2] Shandong Univ, Qilu Hosp, Cheeloo Coll Med, Dept Ophthalmol, Jinan, Peoples R China
[3] Shandong Univ, Shandong Qianfoshan Hosp, Cheeloo Coll Med, Dept Resp, Jinan, Peoples R China
[4] OfJining Med Univ, Yanzhou Branch, Affiliated Hosp, Jining, Peoples R China
来源
JOURNAL OF INFLAMMATION-LONDON | 2022年 / 19卷 / 01期
基金
中国国家自然科学基金;
关键词
Acute lung injury; Intestinal mucosal barrier impairment; Pyroptosis; GSDMD; Disulfiram; Inflammation; MECHANISM;
D O I
10.1186/s12950-022-00313-y
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background Pyroptosis was implicated in acute lung injury (ALI). Disulfiram is reported as an effective pyroptosis inhibitor by inhibiting gasdermin D(GSDMD). However, the function of pyroptosis executor GSDMD and treatment of disulfiramon on ALI, especially whether it was involved in ALI-associated intestinal mucosal barrier impairment remains unclear. This study aims to explore the role of pyroptosis and disulfiram' treatment on ALI and related intestinal mucosal barrier impairment. Methods First, we established lipopolysaccharide (LPS)-induced ALI models in wild-type and Gsdmd knockout (Gsdmd(-/-)), to detect the effect of pyroptosis on ALI-related intestinal mucosal barrier impairment. Furthermore, we used wild-type mice treated with disulfiram to investigate the treatment of disulfiram on ALI and related intestinal mucosal barrier impairment. Results The data showed that GSDMD-mediated pyroptosis was activated in both lung and intestinal mucosa tissues in LPS-induced ALI, and deficiency of Gsdmd ameliorated LPS-induced ALI and related intestinal mucosal barrier damage. We also disclosed that disulfiram inhibited the pyroptosis level, and alleviated ALI and related intestinal mucosal barrier impairment induced by LPS. Conclusion These findings suggested the role of GSDMD-mediated pyroptosis and the potential application treatment of disulfiram in ALI and related intestinal mucosal barrier damage.
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页数:12
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