中国免疫学杂志2025,Vol.41Issue(3):571-575,581,6.DOI:10.3969/j.issn.1000-484X.2025.03.011
PD-1/PD-L1抑制剂对脂多糖诱导的小鼠小胶质细胞炎症反应的作用研究
Effect of PD-1/PD-L1 inhibitors on lipopolysaccharide-induced inflammation in mouse microglia
摘要
Abstract
Objective:To investigate the effect of PD-1/PD-L1 inhibitor BMS-1 on LPS-induced inflammation in mouse microg-lia cells(BV-2 cells).Methods:Bv-2 cells were divided into Control group,LPS group and LPS+BMS-1 group.Bv-2 cells in Control group were cultured in DMEM medium for 78 hours,cells in LPS group were stimulated with 100 ng/ml LPS for 6 hours after 72 hours of normal culture,Bv-2 cells in LPS+BMS-1 group were treated with 50 nmol/ml BMS-1 for 72 hours and then stimulated with 100 ng/ml LPS for 6 hours.Expressions of PD-1 and iNOS mRNA in each group were detected by RT-qPCR,and expressions of PD-1 and iNOS protein in microglia were detected by Western blot.Flow cytometry was used to detect cell apoptosis in each group.Levels of inflamma-tory cytokines IL-1β,IL-6,TNF-α and IL-10 were detected by ELISA.Results:RT-qPCR and Western blot results showed that com-pared with Control group,LPS group had significantly increased expression of PD-1 and iNOS(P<0.05).Compared with LPS group,LPS+BMS-1 group had significantly decreased expression of PD-1(P<0.05)and significantly increased expression of iNOS(P<0.05).Flow cytometry showed that compared with Control group,LPS group had a significantly increased in apoptosis of microglia(P<0.000 1).Compared with LPS group,LPS+BMS-1 group had a significantly increased in apoptosis of microglia(P<0.000 1).ELISA results showed that compared with Control group,LPS group had no significantly increased in pro-inflammatory factors IL-1β and IL-6(P>0.05),while significantly increased in TNF-α(P<0.000 1)and anti-inflammatory factor IL-10(P<0.000 1).Pro-inflammatory cyto-kine IL-1β in LPS+BMS-1 group was significantly higher than that in LPS group(P=0.000 1),IL-6 and TNF-α were also significantly higher than those in LPS group(P<0.000 1),while anti-inflammatory cytokine IL-10 in LPS+BMS-1 group was significantly lower than that in LPS group(P<0.000 1).Conclusion:BMS-1 can promote LPS-induced inflammatory response or impede the recovery of inflammation,and increase apoptosis of microglia.PD-1/PD-L1 pathway may be a potential therapeutic target for neuroinflammation.关键词
神经炎症/小胶质细胞/脂多糖/炎症反应/PD-1/PD-L1Key words
Neuroinflammation/Microglia/Lipopolysaccharide/Inflammatory response/PD-1/PD-L1分类
医药卫生引用本文复制引用
田进杰,王召,郭朝,冯素娟,王蕾,严红燕,胡伟梁,张毅..PD-1/PD-L1抑制剂对脂多糖诱导的小鼠小胶质细胞炎症反应的作用研究[J].中国免疫学杂志,2025,41(3):571-575,581,6.基金项目
江苏省中医药科技发展计划项目(MS2021060) (MS2021060)
南通市科技计划项目(JC2021179,MS12021041) (JC2021179,MS12021041)
南通市卫生健康委员会科研课题(MB2021013,MB2021018,MB2021026). (MB2021013,MB2021018,MB2021026)