脂氧素受体激动剂对巨细胞病毒感染巨噬细胞的免疫负调节  

Negative immunomodulatory effect of lipoxin receptor stimulating agent on macrophages infected by human cytomegalovirus

作　　者：陈晓红[1,2] 舒赛男[1] 刘兴楼[1] 王慧[1] 张菊[1] 杜小弋[1,2] 李革[1] 方峰[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院儿科系,湖北省武汉市430030 [2]武汉市儿童医院,湖北省武汉市430016

出　　处：《中国组织工程研究》2013年第5期886-893,共8页Chinese Journal of Tissue Engineering Research

基　　金：高等学校博士学科点专项科研基金(20090142110076)~~

摘　　要：背景:脂氧素可以抑制炎症细胞、内皮细胞、小鼠脾脏树突状细胞等合成细胞因子,还可以抑制炎性细胞因子对细胞的生物效应。目的:分析脂氧素受体激动剂BML-111对人巨细胞病毒感染THP-1源巨噬细胞的免疫调节作用。方法:用人巨细胞病毒AD169毒株感染THP-1源巨噬细胞(MOI=0.5),细胞培养后设立对照组、人巨细胞病毒感染组及人巨细胞病毒+BML-111组。在感染后0,1,2,4,12,24,48,72h收集各组细胞培养上清液,以ELISA检测各组细胞因子的表达水平;RT-PCR检测各指标mRNA的表达强度;Western blot检测感染4h的细胞核内p65亚基蛋白表达。结果与结论:与对照组相比,其他两组各细胞因子蛋白及mRNA表达明显升高(P<0.05)。与人巨细胞病毒感染组相比,人巨细胞病毒+BML-111组白细胞介素1β和肿瘤坏死因子α显著降低,转化生长因子β显著升高(P<0.05),白细胞介素10差异无显著性意义(P>0.05);人巨细胞病毒+BML-111组各细胞因子mRNA均明显降低(P<0.05)。与对照组相比,其他两组细胞核内NF-κBp65亚基蛋白浓度明显升高(P<0.05);人巨细胞病毒+BML-111组显著低于人巨细胞病毒感染组(P<0.05)。说明BML-111可能通过抑制NF-κB的p65亚基核转位,减少白细胞介素1β、肿瘤坏死因子α的表达,促进转化生长因子β的表达,从而对人巨细胞病毒感染的THP-1源巨噬细胞发挥其免疫负调节作用。BACKGROUND： Lipoxin can inhibit the synthesis of inflammatory cells, endothelial cells and mouse spleen dendritic cells into the cytokines, and it can also inhibit the biological effects of inflammatory cytokines on cells OBJECTIVE： To investigate the negative immunomodulatory effect of lipoxin receptor stimulating agent BML-111 on THP-1 macrophages infected by human cytomegalovirus. METHODS： THP-1 derived macrophages were infected with human cytomegalovirus AD169 （multiplicity of infection=0.5）, and the cultured cells were randomly divided into control group, human cytomegalovirus group and human cytomegalovirus＋BML-111 group. Then the cell culture supemafant was collected at 0, 1, 2, 4, 12, 24, 48 and 72 hours after infection, and the expression levels of cytokines in each group were detected with enzyme-linked immunosorbent assay; mRNA levels of the factors were tested with real-time PCR; Western blot was used to detect the expression of p65 subunit protein in the nucleus after infection for 4 hours. RESULTS AND CONCLUSION： Compared with the control group, the cytokine protein and mRNA expression both in human cytomegalovirus group and human cytomegalovirus＋BML-111 group were increased significantly （P 〈 0.05）. Compared with human cytomegalovirus group, the levels of interleukin-113 and tumor necrosis factor a in human cytomegalovirus＋BML-111 group were decreased significantly, and thus the level of transforming growth factor-13 was increased greatly （P 〈 0.05）. There was no significant difference of the level of interleukin-10 between the two groups （P 〉 0.05） mRNA expression, mRNA expression of all the cytokines in human cytomegalovirus＋BML-11 i group was lower than that in human cytomegalovirus group （P 〈 0.05）. Compared with the control group, the level of p65 subunit protein in the nucleus of human cytomegalovirus group and human cytomegalovirus＋BML-111 group was increased significantly （P 〈 0.05）. The level of p65 subunit protein in the nucleus of human

关 键 词：器官移植 移植与免疫 巨细胞病毒 巨噬细胞 脂氧素 脂氧素受体激动剂 免疫调节 肿瘤细胞坏死因子 其他基金 

分 类 号：R318[医药卫生—生物医学工程]