AUTHOR=Yang Dianyin , Zhao Dongyang , Ji Jinlu , Wang Chunxue , Liu Na , Bao Xiaowei , Liu Xiandong , Jiang Sen , Zhang Qianqian , Tang Lunxian 

TITLE=CircRNA_0075723 protects against pneumonia-induced sepsis through inhibiting macrophage pyroptosis by sponging miR-155-5p and regulating SHIP1 expression

JOURNAL=Frontiers in Immunology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1095457

DOI=10.3389/fimmu.2023.1095457

ISSN=1664-3224

ABSTRACT=Circular RNAs (circRNAs) have been linked to regulate macrophage polarization and subsequent inflammation in sepsis. However, the underlying mechanism and the function of circRNAs in macrophage pyroptosis in pneumonia-induced sepsis are still unknown. In this investigation, we found circ_0075723, a novel circRNA that was significantly downregulated in pneumonia-induced sepsis patients compared to pneumonia patients without sepsis and healthy individuals. Meanwhile, pneumonia-induced sepsis patients exhibited activation of NLRP3 inflammasome and production of the pyroptosis-associated pro-inflammatory cytokines IL-1β and IL-18. circ_0075723 inhibited macrophage pyroptosis via sponging miR-155-5p which promoted SHIP1 expression directly. MiRanda and TargetScan were utilized to identify miR-155-5p binding locations within circ_0075723, and the target connection was verified using dual luciferase assay and RNA pull-down assay. circ_0075723 negatively regulated miR-155-5p expression, and miR-155-5p mimics partially reduced protective impact of circ_0075723 on macrophages pyroptosis. SHIP1 was recognized as a miR-155-5p target gene and circ_0075723 promote SHIP1 expression, while miR-155-5p mimics could effectively suppress SHIP1 upregulation induced by circ_0075723 overexpression. Besides, we found that circ_0075723 in macrophages promoted VE-cadherin expression in endothelial cells through inhibiting the release of NLRP3 inflammasome-related cytokines, IL-1β and IL-18, and subsequently altered endothelial permeability. Collectively, our findings propose a unique approach wherein circ_0075723 suppresses macrophage pyroptosis and inflammation in pneumonia-induced sepsis via sponging with miR-155-5p and promoting SHIP1 expression. These findings indicate that circRNAs could be used as possible potential diagnostic and therapeutic targets for pneumonia-induced sepsis.