中华皮肤科杂志 ›› 2007, Vol. 40 ›› Issue (1): 22-24.

• 论著 • 上一篇    下一篇

氮杂胞苷对SLE患者外周血T细胞Th2细胞因子基因表达的影响

米向斌, 谭国珍, 尹若菲, 曾凡钦   

  1. 广州市, 中山大学第二附属医院皮肤科 510120
  • 收稿日期:2006-04-18 出版日期:2007-01-15 发布日期:2007-01-15
  • 通讯作者: 曾照钦,email:fqzeng@21cn.com E-mail:fqzeng@21cn.com
  • 基金资助:
    广东省卫生厅资助项目(A2003207)

Effects of azacytidine on the gene expression of Th2 cytoldnes in peripheral T cells of patients with systemic lupus erythematosus

MI Xiang-bin, TAN Guo-zhen, YIN Ruo-fei, ZENG Fan-qing   

  1. Department of Dermatology, Second AflFliated Hospital of Sun Yat-sen University, Guangzhou 510120, China
  • Received:2006-04-18 Online:2007-01-15 Published:2007-01-15

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摘要： 目的 探讨DNA甲基化抑制剂氮杂胞昔对sLE患者和正常人外周血T细胞DNA甲基转移酶1和细胞因子IL-4,IL-6,IL-10表达的影响.方法 分离活动期SLE患者(n=15)、非活动期SLE患者(n=13)以及正常人对照(n=14)外周血T细胞,经PHA刺激1天后,分为甲基化抑制组和非抑制组进行培养,分别加人或不加氮杂胞昔继续培养3天;用RT-PCR方法测定各组外周血T细胞IL-4,IL-6,IL-10和DNA甲基转移酶1(Dnmt1)mRNA的表达水平.结果 ①非抑制组内,活动期、非活动期SLE患者的IL-4,IL-6,IL-10mRNA表达均高于正常人对照,DnmtlmRNA表达显著下降,差异有统计学意义(P值均<0.05);并且,活动期、非活动期SLE患者DNA甲基转移酶1的表达一与IL-4,IL-6,IL-10mRNA水平呈负相关(P值均<0.05).②与非抑制组比较,甲基化抑制组中的正常人T细胞IL-4,IL-6,IL-10mRNA表达增加,而Dnmtl表达则明显降低,差异均有统计学意义(P值均<0.05).甲基化抑制组中的活动期、非活动期SLE患者与非抑制组比较,T细胞表达Th2细胞因子、DNA甲基转移酶1表达差异无统计学意义(P值均>0.05).结论 T细胞表达Th2细胞因子与基因组的DNA甲基化程度相关.

关键词: 尖锐湿疣, 外周血单核细胞, Toll样受体, 流式细胞仪, 红斑狼疮,系统性, DNA甲基化, 氮杂胞昔, 白细胞介素4, 白细胞介素6, 白细胞介素10

Abstract: Objective To investigate the effects of DNA methylation inhibitor azacytidine on the gene expression of Th2 cytokines in peripheral T cells of patients with systemic lupus erythematosus(SLE) and healthy controls. Methods Peripheral blood T cells isolated from patients with active SLE(n=15), patients with inactive SLE(n=13),and healthy control individuals(n=14)were stimulated with PHA for 1 d and then cultured an additional 3 d with or without azacytidine. The expression of IL-4, IL-6, IL-10, and DNA methyltransferase 1(Dnmtl)mRNA were detected by semiquantitative reverse transcription polymerase chain reaction(RT-PCR). Results ①In the absence of azacytidine, the gene expression of IL-4, 6, 10 in T cells of patients with active or inactive SLE was significant higher than that in healthy controls(P<0.05),whereas the gene expression of Dnmtl in T cells of patients with active or inactive SLE was significant lower than that in healthy controls(P<0.05).Meanwhile, there was a significant inverse correlation between the expression of IL-4, 6, 10 genes and that of Dnmtl in T cells of SLE patients(P<0.05).②In the presence of azacytidine, T cells of healthy controls expressed a significant higher level of IL-4, 6, 10(P<0.05),and a significant lower level of Dnmtl(P<0.05).Nevertheless, there were no significant changes in the expression of IL-4, 6, 10, and Dnmtl in T cells of patients with active or inactive SLE before and after the treatment with azacytidine(P > 0.05). Conclusion These results suggest that the loss of DNA methylation may play an important role in the aberrant expression of Th2 cytokines in SLE.

Key words: Lupus erythematosus, systemic, DNA Methylation, Azacytidine, Interleukin-4, Interleukin-6, Interleukin-10