Molecular biological mechanisms of mucosal inflammation in H. pylori-induced gastritis

幽门螺杆菌引起的胃炎粘膜炎症的分子生物学机制

• 批准号: 10670496
• 负责人: HIGUCHI Kazuhide
• 金额: $ 1.66万
• 依托单位: Osaka City University
• 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 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670496/
• 关键词: Gastritis; Helicobacter pylori; inflammation; immune response; T cells; cytokines; gastric cancer; costimulatory factor; 胃粘膜傷害; 細胞増殖; アポトーシス; ケモプリベンション; COX-2; ODC; 食事因子; リンパ球; T細胞抗原レセプター; 抗原提示細胞; 胃粘膜; 接着分子; costimulatory factor

Antigen-presenting cells are important in the orchestration of immune responses, and their expression of class II MHC enables them to present antigens to CD4+ T cells, A costimulatory signal is also needed for the activation of T cells. Gastric epithelial cells and another cells in the mucosa scarcely express class II MHC, and the amount is remarkably increases in H. pylori infection. Surface epithelial cells were stained for HLA-DR but not ICAM-1, B7-1, or B7-2. Eluctron microscopy of affected mucosa showed lymphocytes adhering to dendritic cells and macrophage stained for ICAM-1 or B7 or both, perhaps because these were presenting antigens to T cells. These results suggest that dendritic cells and macrophages, not surface epithelial cells, are the antigen-presenting cells in the gastric mucosa of patients with gastritis arising from H. pylori. H. pylori stimulates the production of proinflammatory cytokines such as IL-1β and TNF-α by monocytes. The local production of these cytokines … More is an important cause of gastric mucosal inflammation related to H. pylori. The H. pylori extract stimulated the production of these cytokines. PGE2 inhibited such production and also inhibited the expression of messenger RNA. Inhibition by PG of H. pylori-stimulated production of proinflammatory cytokines by monocytes may account for part of the protective and anti-inflammatory effects of PG on gastric mucosa. Gastric cancer continues to be one of the most common malignancies in the world. Recent reports demonstrate the relationship between H. pylori infection and gastric carcinogenesis in Mongolian gerbils. In an attempt to search for dietary factors affecting H. pylori -associated gastritis, we examined the effects of fish meal on H. pylori -infected animals. Fish meal had markedly enhanced H. pylori-induced gastritis in Mongolian gerbils. These results suggest that development of H. pylori -induced gastritis was affected environmental factors including dietary intake, as well as H. pylori strain diversity and host factors. Less

抗原提呈细胞在免疫应答中起重要作用，其表达的第II类MHC使其能够将抗原递呈给CD4+T细胞，T细胞的激活也需要共刺激信号。胃上皮细胞和粘膜中的另一种细胞几乎不表达II型MHC，且在Hp感染时其数量显著增加。表面上皮细胞表达HLA-DR，但不表达ICAM-1、B7-1或B7-2。受影响的粘膜电子显微镜显示淋巴细胞贴附于树突状细胞和巨噬细胞，ICAM-1或B7或两者均染色，可能是因为这些细胞向T细胞递送抗原。这些结果表明，幽门螺杆菌引起的胃炎患者胃粘膜中的抗原提呈细胞是树突状细胞和巨噬细胞，而不是表面上皮细胞。幽门螺杆菌能刺激单核细胞产生促炎细胞因子，如IL-1、β和肿瘤坏死因子-α。这些细胞因子…的局部产生More是与幽门螺杆菌相关的胃粘膜炎症的重要原因。幽门螺杆菌提取物刺激这些细胞因子的产生。PGE2抑制这种产生，也抑制信使RNA的表达。PG抑制幽门螺杆菌刺激的单核细胞产生促炎细胞因子可能是PG对胃粘膜的保护和抗炎作用的部分原因。胃癌仍然是世界上最常见的恶性肿瘤之一。最近的报道表明，幽门螺杆菌感染与蒙古沙土鼠胃癌的发生有关。为了寻找影响幽门螺杆菌相关性胃炎的饮食因素，我们研究了鱼粉对幽门螺杆菌感染动物的影响。鱼粉对幽门螺杆菌诱导的沙土鼠胃炎有明显的增强作用。这些结果表明，幽门螺杆菌引起的胃炎的发生受环境因素的影响，包括饮食摄入量，以及幽门螺杆菌菌株的多样性和宿主因素。较少

项目成果

Higuchi K, Arakawa T, 他: "Is Helicobacter pylori-negative duodenal ulcer masked by the high prevalence of H.pylori infection in the general population ?"Am J Gastroenterol. 94. 3083-3084 (1999)

Higuchi K、Arakawa T 等人：“幽门螺杆菌阴性十二指肠溃疡是否被普通人群中幽门螺杆菌感染的高患病率所掩盖？” Am J Gastroenterol (1999)。

Wada R, Watanabe T, Nakagawa K, Higuchi K, Arakawa T, Kuroki T, Kaneda K.: "Structure of lamina propria lymphoid follicles and associated epithelium in the gastric mucosa during Helicobacter pylori infection in ulcer-bearing Mongolian gerbils"J Submicrosc

Wada R、Watanabe T、Nakakawa K、Higuchi K、Arakawa T、Kuroki T、Kaneda K.：“溃疡蒙古沙鼠幽门螺杆菌感染期间胃粘膜固有层淋巴滤泡和相关上皮的结构”J Submicrosc

Tominaga K, Higuchi K, 他: "Effect of cultured conditions on morphological changes of Helicobacter pylori"J Gastroenterol. 34. 28-31 (1999)

Tominaga K、Higuchi K 等人：“培养条件对幽门螺杆菌形态变化的影响”J Gastroenterol 34. 28-31 (1999)。

Ohara T, Arakawa T, Higuchi K, et al.: "Overexpression of co-stimudatory mdeciles in peripheval moneruclear cells of Helicobacter pylori-positive peptic ulcer patient: possible difference in host responsiveness compared with non-ulcer patients"Eur. J. Gas

Ohara T、Arakawa T、Higuchi K 等人：“幽门螺杆菌阳性消化性溃疡患者的外周单核细胞中共刺激 mdeciles 的过度表达：与非溃疡患者相比，宿主反应性可能存在差异”Eur。

Higuchi K, Arakawa T, 他: "Eradication of Helicobacter pylori with a Chinese herbal medicine without emergence of resistant colonies"Am J Gastroenterol. 94. 1419-1420 (1999)

Higuchi K, Arakawa T, et al.：“用中草药根除幽门螺杆菌而不出现耐药菌落”Am J Gastroenterol. 94. 1419-1420 (1999)