MAPK^(ERK1/2)信号通路在狼疮肾炎外周血单个核细胞表达白细胞介素-6mRNA中的作用  

Functions of extracellular signal-regulated kinase 1/2 pathway in peripheral blood mononuclear cells over-expression of interleukin-6 mRNA of patients with lupus nephritis

作　　者：张涤华[1] 李幼姬[1] 王俭勤[1] 梁柳琴[2] 黄凌虹[1] 周道远[1] 叶任高[1] 余学清[1] 

机构地区：[1]中山大学附属第一医院肾脏内科,广州510089 [2]中山大学附属第一医院风湿内科,广州510089

出　　处：《中华风湿病学杂志》2005年第6期334-337,共4页Chinese Journal of Rheumatology

基　　金：中山大学211重点科研基金资助项目(98150);中山大学科研基金资助项目(200035)

摘　　要：目的探讨有丝分裂原活化蛋白激酶-细胞外调节激酶1/2(MAPKERK1/2)信号通路在狼疮肾炎(LN)患者外周血单个核细胞(PBMC)中自发高水平表达白细胞介素(IL)-6mRNA中的作用。方法分离培养患者PBMC,利用蛋白免疫印迹法和反转录-聚合酶链反应(RT-PCR)法分别检测MAPKERK1/2磷酸化活化程度和IL-6mRNA表达水平,并与正常人群比较。结果26例LN患者与21名健康对照者比较,LN患者PBMCMAPKERK1/2信号通路呈高度活化状态,体外培养可自发表达高水平IL-6mRNA,两组间差异有统计学意义(P<0.05)。应用特异性阻断剂PD98059阻断LN患者PBMCMAPKERK1/2信号通路活化可显著抑制IL-6mRNA的自发高表达。结论LN患者PBMC中MAPKERK1/2信号通路异常活化,并在PBMC自发高水平表达IL-6mRNA中起作用。Objective To investigate the functional significance of mitogen activating protein kinase-extracellular signal-regulated kinase1/2 (MAPKERK1/2) pathway in spontaneous over-expression of interleukin (IL)-6 mRNA in peripheral blood mononuclear cell (PBMC) from patients with lupus nephritis (LN). Methods Peripheral blood mononuclear cells (PBMC) were obtained and cultured from 26 LN patients and 21 healthy persons. Semi-quantity immunoblot assay and reverse transcriptase PCR (RT-PCR) were used to determine the activation state of MAPKERK1/2 pathway and interleukin (IL)-6 mRNA expression in PBMC respectively. Results Semi-quantity immunoblot assays and RT-PCR demonstrated a significant increase of MAPKERK1/2 activation and IL-6 mRNA expression in PBMC of LN patients when compared with normal PBMC. When blocking the MAPKERK1/2 pathway with specific antagonist PD98059, IL-6 mRNA spontaneous over-expression of PBMC was significantly inhibited. Conclusions MAPKERK1/2 signal transduction pathway plays an important role in spontaneous over-expression of IL-6 in PBMC of LN, which suggests that the abnormal activation of MAPKERK1/2 pathway may mediate the immune abnormalities of LN.

关 键 词：ERK1/2信号通路 狼疮肾炎 白细胞介素-6 细胞表达 有丝分裂原活化蛋白激酶 反转录-聚合酶链反应 外周血单个核细胞 细胞外调节激酶 蛋白免疫印迹法 PD98059 PBMC IL-6 mRNA表达 高水平 分离培养 活化程度 PCR) 正常人群 

分 类 号：R593.242[医药卫生—内科学]