LXR-ABCA1/ABCG1通路对BCG感染的巨噬细胞凋亡和炎性反应的调控作用  

Regulatory effects of LXR-ABCA1/ABCG1 pathway on the apoptosis and inflammatory response of macrophages infected with BCG

作　　者：徐金瑞 郑雪迪 马伯利 杨易 XU Jinrui;ZHENG Xuedi;MA Boli;YANG Yi(Key Laboratory of Conservation and Utilization of Special Biological Resources in West China,Ministry of Education,Ningxia University,Yinchuan 750021,China)

机构地区：[1]宁夏大学西部特色生物资源保护与利用教育部重点实验室,银川750021

出　　处：《免疫学杂志》2022年第5期401-406,共6页Immunological Journal

基　　金：国家自然科学基金项目(31960700,31960712)。

摘　　要：目的揭示LXR-ABCA1/ABCG1通路对BCG感染后巨噬细胞凋亡和炎性反应的调控作用。方法采用T0901317预处理RAW264.7巨噬细胞2 h和BCG感染24 h,设置4个实验组:对照组、T0901317组、BCG感染组和T0901317+BCG感染组。采用Western blot方法检测凋亡相关蛋白cleaved-Caspase3、cleaved-Caspase8、cleaved-Caspase9和TLR信号通路相关蛋白TLR2、TLR4、MyD88、TRAF6、p-NF-κB p65、IRF3、TBK1的表达,采用ELISA方法检测细胞培养上清中促炎细胞因子TNF-α、IL-6、IL-1β的含量。结果与对照组比较,BCG感染组凋亡相关蛋白cleaved-Caspase3、cleaved-Caspase8、cleaved-Caspase9及依赖MyD88途径蛋白TLR2、TLR4、MyD88、TRAF6、p-NF-κBp65的表达均上调(P<0.01),促炎细胞因子TNF-α、IL-6、IL-1β表达水平上升(P<0.01);与BCG感染组相比,T0901317+BCG感染组上述蛋白的表达下调(P<0.01),促炎细胞因子表达水平下降(P<0.01),而MyD88非依赖途径蛋白IRF3、TBK1的表达在各组间差异不显著(P>0.05)。结论激活LXR-ABCA1/ABCG1通路可抑制由BCG感染引起的巨噬细胞凋亡及MyD88途径介导的炎性反应。This study was performed to investigate the regulatory effect of LXR-ABCA1/ABCG1 pathway on apoptosis and inflammatory response of macrophages infected with BCG.Macrophage RAW264.7 cells were recruited and divided into control group,T0901317 group,BCG infected group and T0901317+BCG(pretreated with T0901317 for 2 h and infected by BCG)infected group.Western blot was used to detect the expression levels of apoptotic proteins cleaved-Caspase3,cleaved-Caspase8,cleaved-Caspase9,and TLR signaling pathway related proteins TLR2,TLR4,MyD88,TRAF6,p-NF-κB p65,IRF3,and TBK1.The levels of proinflammatory cytokines TNF-α,IL-6,and IL-1βin the supernatant of cell culture were detected by ELISA.Compared with control group,the expression of apoptosis related proteins cleaved-Caspase3/8/9 and MyD88-dependent pathway proteins TLR2,TLR4,MYD88,TRAF6 and p-NF-κBp65 were up-regulated(P<0.01),while the expression levels of proinflammatory cytokines TNF-α,IL-6,and IL-1βwere increased in BCG group(P<0.01).Compared with BCG group,the expression of the above proteins was down-regulated,and the expression of proinflammatory cytokines were decreased in T0901317+BCG group(P<0.01).MyD88-independent RF3 and TBK1 proteins were not significantly changed among all groups(P>0.05).All these results indicated that activation of LXR-ABCA1/ABCG1 pathway inhibits BCG infection-induced apoptosis and MyD88 pathway-mediated inflammatory responses in macrohages.

关 键 词：LXR-ABCA1/ABCG1通路 RAW264.7细胞 BCG 凋亡 炎性 

分 类 号：R939.91[医药卫生—生药学]