2021 Fiscal Year Final Research Report

Gastric carcinogenesis caused by Helicoobacter pylori-induced inflammation

Research Project

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Project/Area Number	19K07270
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Review Section	Basic Section 48010:Anatomy-related
Research Institution	Oita University
Principal Investigator	Hamada Fumihiko 大分大学, 医学部, 教授 (70252707)
Co-Investigator(Kenkyū-buntansha)	村上和成大分大学, 医学部, 教授 (00239485) 二宮遼大分大学, 医学部, 助教 (00794041) 赤嶺孝祐大分大学, 医学部, 助教 (60799435) 久保修一大分大学, 医学部, 助教 (60898097)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	ピロリ菌 / 炎症性脂質メディエーター / CagA
Outline of Final Research Achievements	Helicobacter pylori infection is known to be a risk factor of stomach cancer. Strains harboring the CagA (cytotoxin-associated gene A) virulence factor strongly stimulate host inflammatory response. However, the mechanisms through which CagA induces prolonged inflammation remain elusive. Based on a genome-wide genetic screen using Drosophila, we discovered a lipid mediator of inflammation was significantly increased by ectopic expression of CagA and by infection of CagA-positive H. pylori in gastric epithelial cells. Furthermore, the increased mediator was released into the surrounding tissues, which may recruit immune cells into sites of infection and promote inflammation. These results suggest that the lipid mediator of inflammation may play a major role in H. pylori-mediated inflammation leading to gastric cancer.
Free Research Field	組織学　微生物学
Academic Significance and Societal Importance of the Research Achievements	ピロリ菌感染、特に CagA 毒素を持つピロリ菌感染では炎症が長く続き、本来の胃粘膜の特性が徐々に失われ、萎縮性胃炎から胃癌の発生へと向かうと考えられている。ピロリ菌感染が炎症を長引かせるメカニズムについては未だ結論が得られていない。本研究では、胃細胞に CagA を発現させたり、CagA 陽性ピロリ菌を感染させたりすると、炎症を促進する脂質メディエーター量が細胞内で顕著に増加し、これが細胞外へも放出されることが明らかになった。薬剤耐性のピロリ菌の出現が広く確認される中、我々の研究成果はピロリ菌感染に対する新たな治療法の開発に結び付くことが期待される。