Novel Biological Activity of Verotoxins: Induction of Cytokines.

维罗毒素的新生物活性：细胞因子的诱导。

• 批准号: 10672120
• 负责人: NATORI Yasuhiro
• 金额: $ 1.92万
• 依托单位: International Medical Center of Japan
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10672120/
• 关键词: Verotoxins; Enterohemorrhagic Escherichia coli; Cytokines; Inestinal epithelial cell

Verotoxin/Shiga toxin (Stx) plays a crucial role in the pathogenesis of hemolytic uremic syndrome (HUS) in patients infected with Enterohemorrhagic Escherichia coli. Stx1 and Stx2 produced by the bacteria are cytotoxic due to their N-glycosidase activity on 28S rRNA. In this study, we have shown that Stx also has the activity to induce the production of proinflammatory cytokines in Caco-2 cells, a intestinal epithelial cell line. Both Stx1 and Stx2 induce mRNAs of IL-8, TNFα, MCP-1, but non-toxic mutant of Stx1 which lacks N-glycosidase activity did not induce the cytokine mRNAs. IL-8 production at the protein level was enhanced by Stx1 and Stx2, but not by the mutant Stx1. In addition, plant toxins such as ricin and modeccin that have the same enzyme activity as Stx showed the cytokine-inducing activity. These results demonstrate that Shiga toxins induce expression and synthesis of cytokines in Caco-2 cells and their N-glyconsidase activity is essential for the induction.

Vero毒素/滋贺毒素（Stx）在肠出血性大肠杆菌感染患者的溶血性尿毒综合征（HUS）的发病机制中起重要作用。由细菌产生的Stx 1和Stx 2由于其对28 S rRNA的N-糖苷酶活性而具有细胞毒性。在这项研究中，我们已经表明，Stx也有活性，以诱导产生促炎细胞因子的Caco-2细胞，肠上皮细胞系。Stx 1和Stx 2均能诱导IL-8、TNFα、MCP-1 mRNA的表达，但Stx 1的无毒突变体（N-糖苷酶活性缺失）不能诱导细胞因子mRNA的表达。IL-8的产生在蛋白质水平上被Stx 1和Stx 2增强，但不是由突变体Stx 1。此外，具有与Stx相同的酶活性的植物毒素如蓖麻毒素和莫德菌素显示出对烟碱的诱导活性。这些结果表明，滋贺毒素诱导Caco-2细胞中细胞因子的表达和合成，并且它们的N-糖苷酶活性对于诱导是必需的。

项目成果

Z. L. Ou: "Transient and Sequential Expression of Chemokine mRNA in glomeruli in Puromycin Aminonucleoside Nephrosis"Nephron. (in press). (2000)

Z. L. Ou：“嘌呤霉素氨基核苷肾病肾小球中趋化因子 mRNA 的瞬时和顺序表达”肾单位。

C.yamasaki et al: "Induction of cytokines in a human colon epithelial call line by Shiga torin-(Stx1)and Stx2 but not by non-taxic mutant Stx1" FEBS Lett.442・2-3. 231-234 (1999)

C.yamasaki 等人：“Shiga torin-(Stx1) 和 Stx2 在人结肠上皮细胞系中诱导细胞因子，但非趋向性突变体 Stx1 不诱导”FEBS Lett.442·2-3 (1999)。

Z. L. Ou: "Transient and Sequential Expression of Chemokine mRNA in glomeruli in Puromycin Aminonuclooside Nephrosis"Nephron. (in press). (2000)

Z. L. Ou：“嘌呤霉素氨基核苷肾病肾小球中趋化因子 mRNA 的瞬时和顺序表达”肾单位。

C.Yamasaki, Yu.Natori, X.-T.Zeng, M.Omura, S.Yamasaki, Y.Takeda and Y.Natori: "Introduction of cytokines in a human colon epithelial cell line by Shiga toxin-1 (Stx1) and Stx2 but not by non-toxic mutant Stx1 which lacks N-glycosidase activity."FEBS Lett.

C.Yamasaki、Yu.Natori、X.-T.Zeng、M.Omura、S.Yamasaki、Y.Takeda 和 Y.Natori：“Shiga toxin-1 (Stx1) 在人结肠上皮细胞系中引入细胞因子