狼疮肾炎PBMC高表达抗DS-DNA抗体和IL-6由MAPK^(ERK1/2)通路介导  

Extracellular signal - regulated kinasel/2 pathway mediates PBMC spontaneous over- expressions of IL-6 and anti-dsDNA antibody in patients with lupus nephritis

作　　者：张涤华[1] 李幼姬[1] 王俭勤[1] 梁柳琴[2] 杨念生[1] 黄锋先[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内科,广东广州510080 [2]中山大学附属第一医院风湿科,广东广州510080

出　　处：《中国病理生理杂志》2005年第12期2474-2478,共5页Chinese Journal of Pathophysiology

基　　金：中山大学211工程基金项目(NO.98150);中山大学科研基金项目(NO.200035)

摘　　要：目的:探讨有丝分裂原激活的蛋白激酶-细胞外调节激酶1/2(MAPKEERK1/2)信号通路在系统性红斑狼疮合并肾炎(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6(IL-6)和抗双链DNA抗体(抗DS -DNA抗体)中的作用。方法:分离培养患者PBMC,利用蛋白免疫印迹法、逆转录PCR法和酶联免疫吸附法分别检测MAPKEHK1/2磷酸化活化程度、IL-6表达和抗DS-DNA抗体水平,并与正常对照组比较。结果:26例LN患者与21 例健康对照者比较,体外培养LN患者PBMC MAPKERK1/2信号通路呈高度活化状态,并自发表达高水平IL-6和抗DS -DNA抗体,组间有显著差异(P<0．05)。应用特异性阻断剂PD98059阻断LN患者PBMC MAPKERK1/2信号通路活化可显著抑制IL-6和抗DS-DNA抗体的自发高表达。结论:LN患者PBMC中MAPKERK1/2信号通路异常活化,并介导 PBMC自发高水平表达IL-6和抗DS-DNA抗体。AIM： To investigate the significance of extraeellular signal- regulated kinase1/2（ MAPK^ERK1/2） pathway in spontaneous over- expression of IL- 6 and anti- dsDNA antibody in the periphery blood mononuclear cells （PBMC） from patients with lupus nephritis （LN）. METHODS： PBMC were obtained and cultured from 26 LN patients and 21 healthy persons. Semiquantity immunoblot, rectrotranscriptase polymerase chain reaction, and ELISA were used to determine the activation state of MAPK^ERK1/2 pathway, IL- 6 and anti - dsDNA antibody expression in PBMC. RESULTS： MAPK^ERK1/2 activation, IL - 6 and anti - dsDNA antibody expression in PBMC of LN patients significantly increased compared with that of normal persons. When the MAPK^ERK1/2 pathway was blocked by a specifie antagonist PD98059, spontaneous expression of IL-6 and anti- dsDNA antibody in LN PBMC were significantly inhibited. CONCLUSION： Abnormal activation of MAPK^ERK1/2 pathway mediates the over- expression of IL- 6 and anti -dsDNA antibody in PBMC of patients with LN, suggesting that MAPK^ERK1/2 pathway may play an important role in the pathogenesis of LN.

关 键 词：狼疮肾炎 信号转导 有丝分裂素激活蛋白激酶类 白细胞介素6 

分 类 号：R363[医药卫生—病理学]