Research for comparison of VacA in H. pylori infectious diseases

VacA在幽门螺杆菌感染性疾病中的比较研究

• 批准号: 14406007
• 负责人: HIRAYAMA Toshiya
• 金额: $ 8.26万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14406007/
• 关键词: Helicobocter pylori; vacuolating cytotoxin; VacA toxin; bacterial toxin; diseases; Toxin comparison; 多形比較; ヘリコバクター・ピロリ感染症; VacA; ヘリコバクター・ピロリ

Persistent infection with Helicobacter pylori causes chronic active gastritis, which predisposes the mucosa to peptic ulceration, and is believed to participate in the pathogenesis of gastric carcinoma and MALT lymphoma. H pylori secretes VacA, a cytotoxin that causes vacuolar degeneration of susceptible cells. Sequence in the middle of VacA defines two families, termed m 1 VacA and m2 VacA, which differ in cell specificity. Since s1/m2 strains produce low levels of toxin, it is likely that m1VacA. is responsible for more epithelial damage than m2VacA.In this study, we purified m 1 VacA and m2VacA from culture medium from H. pylori isolated from patients suffering from H. pylori-induced various diseases in Philippine and Japan.Similar to m1VacA, m2VacA is activated by acid or alkali, thereby enhancing its binding cells, the initial step in vacuole formation in susceptible cells. Immunoprecipitation experiments showed that activated m2VacA, similar to miVacA, binds to two receptor-like protein tyrosine phosphatases, RPTPa and RPTP(3 in AZ-52 1 cells, suggesting that activated m2VacA as well as m1VacA may contribute to gastrointestinal disease following H. pylori infection.Our results. lead that m2VacA is a significant virulence factor and support the finding that H. pylori strains with m2VacA is associated with duodenal ulcer reported by Go et al. [Go, M. F., Cissell, L., and Grayham, D. Y. (1998) Scand. J. Gastroenterol. 33, 132-136].

幽门螺杆菌持续感染会导致慢性活动性胃炎，使粘膜容易发生消化性溃疡，并被认为参与胃癌和MALT淋巴瘤的发病机制。幽门螺杆菌分泌 VacA，一种导致易感细胞空泡变性的细胞毒素。 VacA 中间的序列定义了两个家族，称为 m 1 VacA 和 m2 VacA，它们的细胞特异性不同。由于 s1/m2 菌株产生低水平的毒素，因此很可能是 m1VacA。比 m2VacA 造成更多的上皮损伤。在这项研究中，我们从菲律宾和日本患有幽门螺杆菌引起的各种疾病的患者中分离出的幽门螺杆菌培养基中纯化了 m 1 VacA 和 m2VacA。与 m1VacA 类似，m2VacA 被酸或碱激活，从而增强其与细胞的结合，这是易感细胞中液泡形成的第一步。免疫沉淀实验表明，与 miVacA 类似，在 AZ-52 1 细胞中，活化的 m2VacA 与两种受体样蛋白酪氨酸磷酸酶 RPTPa 和 RPTP(3 结合，表明活化的 m2VacA 和 m1VacA 可能导致幽门螺杆菌感染后的胃肠道疾病。我们的结果表明，m2VacA 是一个重要的毒力因子 并支持 Go 等人报道的带有 m2VacA 的幽门螺杆菌菌株与十二指肠溃疡相关的发现。 [Go, M. F.、Cissell, L. 和 Grayham, D. Y. (1998) Scand。 J.胃肠病学。 33、132-136]。

项目成果

Ohsaki M. et al.: "In Vitro Gene Transfection Using Dendritic Poly(L-Lysine)"Bioconjugate Chem.. 13. 510-517 (2002)

Ohsaki M. 等人：“使用 Dendritic Poly(L-Lysine) 进行体外基因转染”Bioconjugate Chem.. 13. 510-517 (2002)

Mori N et al.: "Helicobacter pylori induces matrix metalloproteinase-9 through activation of nuclear factor kappaB"Gastroenterology. 124. 983-992 (2003)

Mori N 等人：“幽门螺杆菌通过激活核因子 kappaB 诱导基质金属蛋白酶 9”胃肠病学。

Suzuki J.et al.: "Involvement of syntaxin 7 in human gastric epithelial cell vacuolation induced by the Helicobacter pylori-produced cytotoxin VacA."J.Biol.Chem.. 278. 25585-25590 (2003)

Suzuki J.et al.：“幽门螺杆菌产生的细胞毒素 VacA 诱导的人胃上皮细胞空泡形成中突触融合蛋白 7 的参与。”J.Biol.Chem.. 278. 25585-25590 (2003)

Suzuki J, Ohnishi H, Wada A, Hirayama T, Ohno H, Ueda N, Yasuda H, Iiri T, Wada Y, Futai M, Mashima H.: "Involvement of syntaxin 7 in human gastric epithelial cell vacuolation induced by the Helicobacter pylori-produced cytotoxin VacA"J Biol Chem.. 278. 2

Suzuki J、Ohnishi H、Wada A、Hirayama T、Ohno H、Ueda N、Yasuda H、Iiri T、Wada Y、Futai M、Mashima H.：“突触蛋白 7 参与幽门螺杆菌诱导的人胃上皮细胞空泡形成

Mori N et al.: "Helicobacter pylori induces RANTES through activation of NF-kappa B"Infection and Immunity. 71. 3748-3756 (2003)

Mori N 等人：“幽门螺杆菌通过激活 NF-κ B 诱导 RANTES”感染和免疫。