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东亚和西半球幽门螺杆菌之间的 CagL 多态性与诱导 IL-8 分泌的不同能力有关。

CagL polymorphisms between East Asian and Western Helicobacter pylori are associated with different abilities to induce IL-8 secretion.

机构信息

Department of Oral Biology, Oral Science Research Center, Department of Applied Life Science, the Graduate School, BK21 FOUR Project, Yonsei University College of Dentistry, Seoul, 03722, Republic of Korea.

Present address: Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon, 21999, Republic of Korea.

出版信息

J Microbiol. 2021 Aug;59(8):763-770. doi: 10.1007/s12275-021-1136-2. Epub 2021 Jun 1.

Abstract

Helicobacter pylori colonizes human gastric mucosa. Its infection is associated with gastric diseases including gastric cancer. CagA is one of the most important toxins produced by H. pylori. It is related to gastric cancer which can be injected into host cells via a type IV secretion system (T4SS). CagL is a structural component of T4SS apparatus, which triggers host cell signaling pathway. It has been reported that CagL polymorphisms may influence the severity of disease development. To explore the contribution of CagL polymorphisms between East Asian and Western H. pylori in pathogenesis, cagL gene in G27 H. pylori was swapped by K74 cagL which is identical to East Asian CagL consensus sequence and by Western 26695 H. pylori, resulting in G27 ΔcagL/cagL and G27 ΔcagL/cagL, respectively. Intriguingly, G27 ΔcagL/cagL showed significantly less ability of IL-8 induction than G27 ΔcagL/cagL while displayed similar abilities of CagA phosphorylation, and cell elongation. Taken together, this study suggests that the CagL polymorphism may influence IL-8 induction, and K74 CagL has less ability to induce IL-8 secretion than G27 or 26695 CagL. Further research should address how the different capabilities of IL-8 induction between intraspecies-CagL are associated with the large differences of the incidence of gastric cancer between East Asian and Western countries.

摘要

幽门螺杆菌定植于人类胃黏膜。其感染与包括胃癌在内的多种胃部疾病相关。CagA 是幽门螺杆菌产生的最重要的毒素之一。它与胃癌相关,可通过 IV 型分泌系统(T4SS)注入宿主细胞。CagL 是 T4SS 装置的结构组成部分,可触发宿主细胞信号通路。据报道,CagL 多态性可能影响疾病发展的严重程度。为了探讨东亚和西方幽门螺杆菌 CagL 多态性在发病机制中的作用,将 G27 幽门螺杆菌的 cagL 基因用与东亚 CagL 一致的 K74 cagL 取代,或用西方 26695 幽门螺杆菌取代,分别得到 G27 ΔcagL/cagL 和 G27 ΔcagL/cagL。有趣的是,与 G27 ΔcagL/cagL 相比,G27 ΔcagL/cagL 诱导 IL-8 的能力显著降低,但 CagA 磷酸化和细胞伸长的能力相似。综上所述,本研究提示 CagL 多态性可能影响 IL-8 的诱导,而 K74 CagL 诱导 IL-8 分泌的能力低于 G27 或 26695 CagL。进一步的研究应探讨同种 CagL 之间诱导 IL-8 能力的差异如何与东亚和西方国家胃癌发病率的巨大差异相关。

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