p38丝裂原活化蛋白激酶信号调控脂多糖所致程序性死亡配体1表达介导免疫麻痹研究  

A study on regulating immune paralysis of PD-L1 expression caused by LPS by p38 MAPK signaling

作　　者：王方[1] Wang Fang

机构地区：[1]南阳医学高等专科学校基础医学部,河南南阳473003

出　　处：《中医临床研究》2020年第31期7-9,共3页Clinical Journal Of Chinese Medicine

基　　金：河南省基础与前沿技术研究计划项目(No.152300410018);南阳市科技攻关计划项目(No.KJGG2018095;2019KJGG118)资助。

摘　　要：目的:探讨脂多糖(Lipopolysaccharide,LPS)调控树突状细胞(Dendritic Cell,DCs)免疫共抑制分子程序性死亡配体1(Programmed Death-Ligand 1,PD-L1)表达介导免疫麻痹的机制。方法:以LPS刺激小鼠DCs建立脓毒血症免疫麻痹体系,采用流式细胞术和BrdU细胞增殖实验分别检测LPS所致树突状细胞PD-L1表达和抗原特异性T细胞增殖反应。结果:LPS显著上调DCs免疫共抑制分子PD-L1表达,并抑制DCs介导的T淋巴细胞增殖反应(P<0.0001)。p38丝裂原活化蛋白激酶(Mitogen-activated Protein Kinase,MAPK)抑制剂——SB203580能显著降低LPS所致PD-L1的高水平表达。SB203580和PD-L1封闭抗体均能显著逆转DCs介导的T淋巴细胞增殖反应的抑制现象(P<0.0001)。结论:LPS上调DCs免疫共抑制分子PD-L1是T细胞免疫反应低下麻痹的主要原因。阻断p38 MAPK信号有助于改善脂多糖所致PD-L1高表达介导的树突状细胞免疫麻痹。Objective:To investigate the mechanism of LPS regulating immune paralysis of PD-L1 expression on DCs.Methods:Immune paralysis of sapremia mice was established by LPS to stimulate DCs.The PD-L1 expression and antigen-specific T cell proliferation response were detected by flow cytometry and BrdU cell proliferation assay,respectively.Results:LPS can significantly increase the PD-L1 expression on DCs,and inhibited the DCs-mediated T lymphocyte proliferation response(P<0.0001).SB203580(p38 MAPK inhibitor)can significantly reduce high levels of PD-L1 expression caused by LPS.SB203580 and PD-L1 blocking antibodies significantly reversed the inhibition of DCs mediated T lymphocytes proliferation response(P<0.0001).Conclusion:The main cause of T cell immunosuppression or immune paralysis was high expression of PD-L1 on DCs induced by LPS.Blocking p38 MAPK signaling maybe improve the DCs immune paralysis causing by PD-L1 high-expression induced by LPS.

关 键 词：程序性死亡配体1 脂多糖 脓毒症 p38丝裂原活化蛋白激酶信号 免疫麻痹 

分 类 号：R967[医药卫生—药理学]