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Role of Helicobacter pylori cytotoxin in the gastric mucosa

幽门螺杆菌细胞毒素在胃粘膜中的作用

基本信息

批准号：
08670611
负责人：
ARAKAWA Tetsuo
金额：
$ 1.47万
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：
1996
资助国家：
日本
起止时间：
1996 至 1998
项目状态：
已结题

项目摘要

Helicobacter pylori infection in the gastric mucosa is strongly associated with chronic type B gastritis and peptic ulcer disease. However the pathogenic mechanisms of the H.pylori related disease is not known. Cytotoxin, which is produced by H.pylori and induces vacuolization in the target cells, is one of the major causative factors. In this research project, we focused on the role of the H.pylori cytotoxin in the gastric mucosa and examined whether H.pylori cytotoxin affects proliferation of the gastric cells and inflammatory cytokine production such as interleukin-1 beta (IL-1beta) and tumor necrosis factor- alpha (TNF- alpha) by human monocytes. We found that 1) H.pylori cytotoxin inhibited growth and proliferation of phuman gastric cultured cells and interferes with epidermal growth factor (EGF) binding to its receptor on the cell surface. 2) H.pylori stimulated inflammatory cytokine production and expression of messenger RNA by human isolated monocytes. 3) Prostaglandin E_2, which plays a central role in the gastric mucosal defense, inhibited H.pylori-induced inflammatory production by human monocytes. 4) These inflammatory cytokine induced gastric ulcer recurrence through increased expression of adhesion molecules and neutrophil infiltration in the rat experimental models and induced MCP-1 expression at the ulcer margin. 5) Interleukin-8 which is high concentration in the H.pylori infected gastric mucosa stimulated intraepithelial margination of neutrophils and impaired epithelial barrier function in the in vitro models. 6) Immunohistochemical study using human biopsy specimens of the H.pylori infected mucosa showed increased expression of ICAM-1, LFA-1, and Mac-1 in the gastric mucosa. These findings contributes pathogenesis of H.pylori related disease and the role of H.pylori cytotoxin in the gastric mucosa.

胃粘膜中幽门螺杆菌感染与慢性B型胃炎和消化性溃疡疾病密切相关。然而，幽门螺杆菌相关疾病的致病机制尚不清楚。由幽门螺杆菌产生的细胞毒素可诱导靶细胞空泡化，是主要的致病因素之一。在本研究项目中，我们关注幽门螺杆菌细胞毒素在胃粘膜中的作用，并检测幽门螺杆菌细胞毒素是否影响胃细胞的增殖和人单核细胞产生的炎性细胞因子，如白细胞介素-1 β（IL-1 β）和肿瘤坏死因子-α（TNF-α）。结果发现：1）幽门螺杆菌细胞毒素抑制人胃粘膜细胞的生长和增殖，并干扰表皮生长因子（EGF）与细胞表面EGF受体的结合; 2)幽门螺杆菌刺激炎症细胞因子的产生和表达的信使RNA的人分离的单核细胞。3)前列腺素E_2在胃粘膜防御中起重要作用，它能抑制幽门螺杆菌诱导的人单核细胞炎症反应。4)这些炎性细胞因子通过增加大鼠实验模型中粘附分子的表达和中性粒细胞浸润诱导胃溃疡复发，并诱导溃疡边缘MCP-1表达。5)幽门螺杆菌感染的胃粘膜中高浓度的白细胞介素8刺激了中性粒细胞的上皮内边集，并损害了体外模型中上皮屏障功能。6)免疫组织化学研究显示，在胃粘膜中ICAM-1、LFA-1和Mac-1的表达增加。这些发现有助于幽门螺杆菌相关疾病的发病机制和幽门螺杆菌细胞毒素在胃粘膜中的作用。