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

Abstract
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 PANoptosis-like 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.
AuthorsYu-Qiong He, Jiu-Ling Deng, Can-Can Zhou, Sheng-Gui Jiang, Feng Zhang, Xia Tao, Wan-Sheng Chen
JournalInternational immunopharmacology (Int Immunopharmacol) Vol. 125 Issue Pt B Pg. 111161 (Dec 2023) ISSN: 1878-1705 [Electronic] Netherlands
PMID37948864 (Publication Type: Journal Article)
CopyrightCopyright © 2023 Elsevier B.V. All rights reserved.
Chemical References
  • Ursodeoxycholic Acid
  • Sting1 protein, mouse
  • Membrane Proteins
Topics
  • Sepsis (complications, drug therapy)
  • Ursodeoxycholic Acid (therapeutic use)
  • Acute Lung Injury (drug therapy, etiology)
  • Male
  • Animals
  • Mice
  • Mice, Inbred C57BL
  • Cell Death
  • Membrane Proteins (metabolism)
  • Inflammation
  • Oxidative Stress

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