Liver X receptor agonist GW3965 protects against sepsis by promoting myeloid derived suppressor cells apoptosis in mice.
发布时间：2021-06-02
点击次数：
影响因子：3.647
发表刊物：Life Sci
关键字：SepsisMDSCsLXRImmunosuppressionABCA1
摘要：Aims Immunosuppressive myeloid-derived suppressor cells (MDSCs) continuously expand and lead to poor outcome during sepsis. The activation of liver X receptor (LXR) can mitigate sepsis-induced liver and myocardial damage. This study aims to determine whether LXR plays a protective role in sepsis by regulating MDSCs. Main methods Cecal ligation and puncture(CLP)was used to induce sepsis in mice. The mice were then treated with LXR agonist GW3965 (3 mg/kg) or vehicle 1 h, 6 h, 12 h, 24 h, 48 h, 72 h postoperatively. The effect of LXR on the survival rate and multi-organ injury induced by sepsis was evaluated by survival analysis, histological staining, biochemical analysis and ELISAs. The percentages of MDSCs and T cells were detected using flow cytometry. The mRNA expressions of LXR and ATP-binding cassette transporter A1 (ABCA1) were measured using real-time quantitative PCR (RT-qPCR). ABCA1 protein level was determined using immunofluorescence staining. Key findings LXR agonist GW3965 treatment improved the survival of septic mice, accompanied by reduced multi-organ injury and a decreased level of inflammatory cytokines. Furthermore, GW3965 treatment decreased MDSCs abundance in spleen by boosting the apoptosis of spleen MDSCs, therefore ameliorating their immunosuppressive activity. Meanwhile, bacteria clearance in tissues was enhanced after the GW3965 administration in septic mice. Mechanistically, GW3965 activated LXRβ and its downstream target ABCA1 to initiate the apoptosis of spleen MDSCs. Significance These findings provide new insights into the relationship between LXR and MDSCs in sepsis, thus revealing a potentially effective approach to target the immunosuppression of sepsis.
合写作者：Yuexue Zhou,Jie Hu,Caiyan Li,Ke Liu,Meidong Liu,Yaxi Zhu
第一作者：Minjie Luo, Wenqin Zhang
论文类型：基础研究
通讯作者：Huali Zhang（通讯作者）, Huan Chen
学科门类：医学
一级学科：基础医学
期号：2021, 276(10141):119434.
是否译文：否
发表时间：2021-03-27
收录刊物：SCI