张华莉

教授 博士生导师 硕士生导师

入职时间:1997-07-09

所在单位:基础医学院

学历:博士研究生毕业

办公地点:湘雅老校区第二教学楼5楼

性别:女

联系方式:15607310187

学位:医学博士学位

在职信息:在职

主要任职:湖南省脓毒症转化医学重点实验室学术委员会副主任,湖南省病理生理学会副理事长,危重病专业委员会副主任委员,中国病理生理学会常务理事

毕业院校:中南大学

学科:基础医学

曾获荣誉:

2013-06-01  当选:  中南大学“升华学者”特聘教授

2013-06-01  当选:  湖南省自然科学杰出青年基金获得者

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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:

发表时间:2021-03-27

收录刊物:SCI

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