Project/Area Number |
07457045
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Human pathology
|
Research Institution | Tohoku University |
Principal Investigator |
NAGURA Hiroshi Tohoku Univ., Sch., Med., Professor, 医学部, 教授 (90022821)
|
Co-Investigator(Kenkyū-buntansha) |
CHIBA Toshio Tohoku Univ., Hp., Lecturer, 医学部・附属病院, 講師 (20171944)
SASAKI Iwao Tohoku Univ., Sch., Med., Associate Professor, 医学部, 助教授 (60125557)
SASANO Hironobu Tohoku Univ., Sch., Med., Research Associate, 医学部, 助手 (50187142)
OHTANI Haruo Tohoku Univ., Sch., Med., Associate Professor, 医学部, 助教授 (30133987)
KIMURA Noriko Tohoku Univ., Sch., Med., Associate Professor, 医学部, 助教授 (80142975)
|
Project Period (FY) |
1995 – 1997
|
Project Status |
Completed (Fiscal Year 1997)
|
Budget Amount *help |
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥3,100,000 (Direct Cost: ¥3,100,000)
|
Keywords | Mucosal immune system / Gastro-intestinal mucosa / Neuropeptide / Inflammatory bowel disease / Chronic gastritis / Macrophage / Hypothalamus / Steroid hormone / 中枢神経系 / 内分泌系 / ウロコルチン / 消化管悪性腫瘍 / 粘膜免疫 / VIP / VIP受容体 / アトピー性皮膚炎 / 潰瘍性大腸炎 / 先天性胆道閉鎖症 / IL-6 |
Research Abstract |
The aim of this study is to clarify the mechanism for interations between the neuroendocrine system and the mucosal immune system, and also to understand roles of abnormalities of the neuroendocrine-immune interactions in the pathogenesis of inflammatory and neoplastic disorders in the gastrointestinal mucosa. 1) Urocortin, a neuropeptide of CRF family showing some physiological CRF-mediated actions in vivo, was localized in macrophages is the lamina propria of the intestnial mucosa, and these macrophages were increased in the inflammatory disotders. This suggests that hormons in the PHA axis play a immunoregulatory roles in the gastrointestinal mucosa, together with cytokines. 2) The majority of neurons of the mucosal and submucosal plexus contained VIP,and its mRNA was found in intraepithelial endocrine cells. VIP is known to regulate macrophage funcions as well as water secretion in the intestine. In inflammatory mucosal lesions, distribution of VIP neurons became irregular and decreased in the number. In addition, appearance of VIP receptor on marophages and dendritic cells in the intestiral mucosa deteriorated in the intestinal mucosa from the infants with food allergy combined with atpic dermatitis. 3) Mineralocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type II were expressed in the same cells participating ion and /or water transport including colonic epithelial cells. Their expression disappeared in regenerating cells in the colonic mucosa with ulcerative colitis. This suggests that the disturbance of ion and water vlance in the ulcerative colitis is caused by the absence of their expression. 4) Foveolar epithelial cells of H.pylori-infected gastric mucosa showed some DNA abnormalities incleding apoptosis induced by macrophage and neutropic infiltration. VIP-neurons became irregular and were decreased.
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