Ursodeoxycholic acid alleviates sepsis-induced lung injury by blocking PANoptosis via STING pathway

被引:21
作者
He, Yu-qiong [1 ,2 ]
Deng, Jiu-ling [3 ]
Zhou, Can-can [4 ]
Jiang, Sheng-gui [2 ]
Zhang, Feng [1 ,2 ]
Tao, Xia [1 ,2 ]
Chen, Wan-sheng [1 ,2 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Inst Chinese Mat Mad, Shanghai 201203, Peoples R China
[2] Second Mil Med Univ, Changzheng Hosp, Dept Pharm, Shanghai 200003, Peoples R China
[3] Fudan Univ, Shanghai Peoples Hosp 5, Dept Pharm, Shanghai 200240, Peoples R China
[4] Tongji Univ, Shanghai Peoples Hosp 10, Dept Pharm, Sch Med, Shanghai 200040, Peoples R China
基金
中国国家自然科学基金;
关键词
UDCA; Acute lung injury; PANoptosis; STING pathway; DYSFUNCTION;
D O I
10.1016/j.intimp.2023.111161
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Acute lung injury (ALI), a progressive lung disease mostly caused by sepsis, is characterized by uncontrolled inflammatory responses, increased oxidative stress, pulmonary barrier dysfunction, and pulmonary edema. Ursodeoxycholic acid (UDCA) is a natural bile acid with various pharmacological properties and is extensively utilized in clinical settings for the management of hepatobiliary ailments. Nonetheless, the potential protective effects and mechanism of UDCA on sepsis-induced lung injuries remain unknown. In this study, we reported that UDCA effectively inhibited pulmonary edema, inflammatory cell infiltration, pro-inflammatory cytokines production, and oxidative stress. Furthermore, UDCA treatment significantly alleviated the damage of pulmonary barrier and enhanced alveolar fluid clearance. Importantly, UDCA treatment potently suppressed PANoptosislike cell death which is demonstrated by the block of apoptosis, pyroptosis, and necroptosis. Mechanistically, UDCA treatment prominently inhibited STING pathway. And the consequential loss of STING substantially impaired the beneficial effects of UDCA treatment on the inflammatory response, pulmonary barrier, and PANoptosis. These results indicate that STING plays a pivotal role in the UDCA treatment against sepsis-induced lung injury. Collectively, our findings show that UDCA treatment can ameliorate sepsis-induced lung injury and verified a previously unrecognized mechanism by which UDCA alleviated sepsis-induced lung injury through blocking PANoptosis-like cell death via STING pathway.
引用
收藏
页数:13
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