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THE PATHOGENETICAL ROLE OF VIRUS INFECTION AND ACTIVATION OF ONCOGENES.

病毒感染和癌基因激活的致病作用。

基本信息

批准号：
02454220
负责人：
HOSHINO Takashi
金额：
$ 2.56万
依托单位：
Fukui Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1990
资助国家：
日本
起止时间：
1990 至 1992
项目状态：
已结题

项目摘要

In order to clarify the role of virus infection and subsequent activation of protooncogenes on the triggering process of collagen disease,, the sera from 66 patients with SLE were analyzed by the immunoblotting method to detect antibodies to the antigens on the EB virus genome positive Raji and P3HR-1 cells, as well as on the cultured myeloid cell lines of various stages of differentiation. The sera from SLE patients were found to contain the antibodies to the antigens with Mr of 66K, 70K, 90K, 140K and 160K daltons on Raji cells which were identified as c-myc protein and EB virus nuclear antigen (EBNA) subtypes 1, 2, 3 and 4, respectively. The frequency and amount of antibodies against EBNA-2 and -3 were significantly higher than in 60 control normal sera. Further, the sera from SLE patient were found to have the antibodies to the antigens with Mr of 60K on K-562, KG-1 and HL-60 cells, which are also known to be c-myc product. After an incubation of HL-60 cells with TPA or vitamin D3 to induce their macrophage differentiation, the SLE sera became to detect the 55K and 39K antigens on the differentiated HL-60 cells, while the 60K antigen turned to undetectable or only faintly detected. Polyclonal antibodies to myc-specific and fos-specific peptides were applied to react with these antigens including cross experiments. The results of these studies confirmed that the sera from SLE patients contain antibodies to c-myc, c-fos and possibly c-Jun/AP-1 protooncogen products. In addition, SLE patients were found to show EBNA positive B cells at 3 times higher frequencies than that of B cells from normal subjects. It was suggested that EB virus infection with subsequent activation of several oncogenes may have an important pathogenetical role on the triggering process of SLE.

为了阐明病毒感染和随后的原癌基因激活在胶原病触发过程中的作用，采用免疫印迹法分析了66例SLE患者血清，以检测EB病毒基因组阳性Raji和P3 HR-1细胞以及培养的不同分化阶段的髓系细胞系上的抗原抗体。SLE患者血清中含有抗Raji细胞表面Mr 66 K、70 K、90 K、140 K和160 K抗原的抗体，分别鉴定为c-myc蛋白和EB病毒核抗原（EBNA）1、2、3和4亚型。抗EBNA-2和-3抗体的频率和数量显着高于60份对照正常血清。此外，发现来自SLE患者的血清具有针对K-562、KG-1和HL-60细胞上的Mr为60 K的抗原的抗体，所述抗原也已知是c-myc产物。用TPA或维生素D_3诱导HL-60细胞向巨噬细胞分化后，SLE血清可检测到分化的HL-60细胞表面的55 K和39 K抗原，而60 K抗原则变为检测不到或仅微弱检测到。应用针对myc特异性肽和fos特异性肽的多克隆抗体与这些抗原反应，包括交叉实验。这些研究的结果证实，SLE患者的血清含有c-myc，c-fos和可能的c-Jun/AP-1原癌基因产物的抗体。此外，发现SLE患者显示EBNA阳性B细胞的频率比来自正常受试者的B细胞的频率高3倍。提示EB病毒感染后多种癌基因的激活可能在SLE的发病过程中起重要作用。