A phytomedicine extract exerts an anti-inflammatory response in the lungs by reducing STING-mediated type I interferon release

作者：Sheng Zhang, Rongrong Huang, Junsong Jing, Xueping Wei, Yu Zhang, Youping Wu, Guoteng Ou, Jingjin Hu, Yueguo Wu, Yuanyuan Li, Shibo Ying, Zhenqiang You · 发表于：Phytomedicine · 年份：2024 · DOI：10.1016/j.phymed.2024.155373 · 被引用次数：11 · 研究领域：interferon and immune responses、Inflammasome and immune disorders、Immune Response and Inflammation

BACKGROUND: Acute respiratory distress syndrome (ARDS) is an acute respiratory disease characterized by bilateral chest radiolucency and severe hypoxemia. Quzhou Fructus Aurantii ethyl acetate extract (QFAEE), which is prepared from the traditional Chinese respiratory anti-inflammatory natural herb Quzhou Fructus Arantii, has the potential to alleviate ARDS. In this work, we aimed to investigate the potential and mechanism underlying the action of QFAEE on ARDS and how QFAEE modulates the STING pathway to reduce type I interferon release to alleviate the inflammatory response. METHODS: mice could explain the STING-targeted effect of QFAEE on alleviating the inflammatory response. Our explorations covered several techniques, Western blot, histological assays, immunofluorescence staining, transcriptomic assays and qRT-PCR to determine the potential mechanism of action of QFAEE in antagonizing the inflammatory response in the lungs, as well as the mechanism of action of QFAEE in targeting the STING signaling pathway to regulate the release of type I interferon. RESULTS: QFAEE effectively alleviates ARDS symptoms in LPS-induced ARDS. We revealed that the mechanism underlying LPS-induced ARDS is the STING-TBK1 signaling pathway and further elucidated the molecular mechanism of QFAEE in the prevention and treatment of ARDS. QFAEE reduced the release of type I interferons by inhibiting the STING-TBK1-IRF3 axis, thus alleviating LPS-induced pneumonia and lung cell death in mice. Anot...