Elucidation of pathophysiology for various digestive diseases

阐明各种消化系统疾病的病理生理学

基本信息

批准号：
15209024
负责人：
CHIBA Tsutomu
金额：
$ 25.63万
依托单位：
Kyoto University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2005
项目状态：
已结题

项目摘要

In this study, we tried to elucidate pathophysiology of H.pylori-induced gastyritis, autoimmune pancreatitis (AIP) and inflammatory bowel disease (IBD) all of which involve immunological responses, and the following results were obtained. (1)In human, patients with gastric ulcer had Th1-predominant immunological response, whereas patients with duodenal ulcer were more polarized to Th2 response. Moreover, in patients with MALT lymphoma, Th2 reaction was remarkable. (2)In mice, severe gastritis developed by HP infection in C57black mice, a typical Th1-type strain, whereas no gastritis could be observed in Balb/c mice, a typical Th2-type strain. On the other hand, by thymectomy, severe gastritis seen in C57black mice disappeared and MALT lymphoma developed in Balb/c mice. Moreover, for MALT lymphoma B cell growth in vitro, in addition to HP presence of HP specific T cells and peripheral blood DC were essential. (3)By using serum of the patient who was negative for anti CAII antibody or anti-lactoferin but with high serum IgG titer, we identified pancreatic trypsin inhibitor as a candidate target for autoantibody in patients with autoimmune pancreatitis. (4)In patients with IBD, serum titiers for anti-Mycobacterium antibody was significantly higher than normal subjects, and involvement of Mycobacterium paratuberculosis infection in pathophysiology of human IBD was suggested. (5)Moreover, involvement of CMV as well as EBV infection in the pathophysiology of IBD was also suggested, and importance of measurement of and comparison of copy numbers of CMV gene in both affected and non-affected colonic site for diagnosis of CMV infection in patients with IBD was indicated. (6)For development of IBD, abnormality of permeability of epithelial barrier and that of regeneration of the epithelium were found to be involved. Accordingly, administration of growth factors such as bFGF, that enhances repair of epithelial cells appeared to be effective for the treatment of IBD.

在本研究中，我们试图阐明幽门螺杆菌引起的胃炎、自身免疫性胰腺炎（AIP）和炎症性肠病（IBD）的病理生理学，这些疾病都涉及免疫反应，并获得了以下结果。 (1)在人类中，胃溃疡患者的免疫反应以Th1为主，而十二指肠溃疡患者的免疫反应则更倾向于Th2反应。而且，在MALT淋巴瘤患者中，Th2反应显着。 (2)在小鼠中，典型Th1型品系C57black小鼠因HP感染而出现严重胃炎，而典型Th2型品系Balb/c小鼠未观察到胃炎。另一方面，通过胸腺切除术，C57black 小鼠中出现的严重胃炎消失，Balb/c 小鼠中出现 MALT 淋巴瘤。此外，对于MALT淋巴瘤B细胞的体外生长，除了HP之外，HP特异性T细胞和外周血DC的存在也是必不可少的。 (3)通过使用抗CAII抗体或抗乳铁蛋白阴性但血清IgG滴度较高的患者血清，我们确定胰腺胰蛋白酶抑制剂作为自身免疫性胰腺炎患者自身抗体的候选靶点。 (4)IBD患者血清抗分枝杆菌抗体滴度明显高于正常人，提示副结核分枝杆菌感染参与人类IBD的病理生理学过程。 (5)此外，还提出了CMV和EBV感染参与IBD的病理生理学，以及测量和比较受影响和未受影响结肠部位的CMV基因拷贝数对于诊断IBD中CMV感染的重要性。患有 IBD 的患者被指出。 (6)IBD的发生与上皮屏障通透性异常和上皮再生异常有关。因此，施用增强上皮细胞修复的生长因子（例如bFGF）似乎对治疗IBD有效。

项目成果

期刊论文数量（124）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nishi T, Chiba T, et al.: "Involvement of myeloid dendritic cells in the development of gastric secondary lymphoid foliicles in Helicobacter pylori-infected BALB/c mice with neonatal thymectomy"Infect Immun. 71. 2153-2162 (2003)

Nishi T、Chiba T 等人：“在新生胸腺切除术中，幽门螺杆菌感染的 BALB/c 小鼠中骨髓树突状细胞参与胃次级淋巴滤泡的发育”。

DOI：
发表时间：
期刊：
影响因子：
0
作者：
通讯作者：

Involvement of myeloid dendritic cells in the development of gastric secondary lymphoid follicles in Helicobacter pylori-infected BALB/c mice with neonatal thymectomy.

骨髓树突状细胞参与新生胸腺切除术的幽门螺杆菌感染的 BALB/c 小鼠胃次级淋巴滤泡的发育。

DOI：
发表时间：
2003
期刊：
Infect Immun 71
影响因子：
0
作者：
Nishi T;Okazaki K;Chiba T;et al.
通讯作者：
et al.

Specific antibodies against recombinant protein of insertion element 900 of Mycobacterium avium subspecies paratuberculosis in Japanese patients with Crohn's disease.

日本克罗恩病患者体内针对副结核分枝杆菌亚种插入元件 900 重组蛋白的特异性抗体。

DOI：
发表时间：
2006
期刊：
Inflamm Bowel Dis 12
影响因子：
0
作者：
Nakase H;Nishio A;Chiba T;et al.
通讯作者：
et al.

REG Ia protein may function as a trophic and/or anti-apoptitic factor in the development of gastric cancer.

REG Ia 蛋白可能在胃癌的发展中充当营养和/或抗凋亡因子。

DOI：
发表时间：
2005
期刊：
Gastroenterology 128
影响因子：
0
作者：
Sekikawa A;Fukui H;Chiba T;et al.
通讯作者：
et al.

Involvement of myeloid dendritic cells in the development of gastric secondary lymphoid follicles in Helicobacter pylori-infected neonatal thymectomized BALB/c mice.

骨髓树突状细胞参与幽门螺杆菌感染的新生胸腺切除 BALB/c 小鼠胃次级淋巴滤泡的发育。

DOI：
发表时间：
2003
期刊：
Infect Immun 71
影响因子：
0
作者：
Nishi T;Okazaki K;Kawasaki K;Fukui T;Tamaki H;Matsuura M;Asada M;Watanabe T;Uchia K;Watanabe N;Nakase H;Ohana M;Hiai H;Chiba T
通讯作者：
Chiba T