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Closs talk between neuroendocrine and mucosal immune systems in the gastrointestinal mucosa and its disorder

Research Project

Project/Area Number 07457045
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Human pathology
Research InstitutionTohoku 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)
KeywordsMucosal 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.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (34 results)

All Other

All Publications (34 results)

  • [Publications] 笹野 公伸, 名倉 宏: "Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma." Am.J.Pathol.151. 821-829 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 木村 伯子, 名倉 宏: "Plasama chromograin A in pheochromocyatma,catecholamine,parathyroid hormone and pituitary hormones." Endocr.J.44. 319-327 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 大谷 明夫, 名倉 宏: "Expression of costimulatory molecules B7-1 and B7-2 in macrophages and granulomas ofCrohn's disease : Demonstration of cell to cellcontact with T lymphocyces." Lab.Invest.77. 175-184 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 笹野 公伸, 名倉 宏: "Ultrastructural and confocal lase scanning microscopiod examinaion of TUNEL positivisells." J.Pathol.181. 235-242 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 笹野 公伸, 名倉 宏: "Colocalization of 11 β-hydroxysteroid dehydrogenase type II and mineralocorticoidreceptor in human epithelia." J.Clin.Endocr.Metabol.82. 3859-3863 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 笹野 公伸, 名倉 宏: "Immunohistochemical study of DNA topoicomerase II in human gastric disorders." Am.J.Pathol.149. 997-1007 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 名倉 宏、木村 伯子: "Essentials of Mucosal Immunology(分担)" Academic Press, 598 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sasano H,Nagura H.: "Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma." Am.J.Pathol.151. 821-829 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Kimura N,Nagura H.: "Plasama chromograin A in pheochromocyatma, catecholamine, parathyroid hormone and pituitary hormones." Endocr.J.44. 319-327 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Ohtani H,Nagura H.: "Expression of costimulatory molecules B7-1 and B7-2 in macrophages and granulomas of Crohn's disease : Demonstration of cell to cell contact with T lymphocytes." Lab.Invest.77. 175-184 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sasano H,Nagura H.: "Ultrastructural and confocal lase scanning microscopiod examination of TUNEL positivi cells." J.Pathol.181. 235-242 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sasano H,Nagura H.: "Colocalization of 11 beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human epithelia." J.Clin.Endocr.Metabol.82. 3859-3863 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sasano H,Nagura H.: "Immunohistochemical study of DNA topoisomerase II in human gastric disorders." Am.J.Pathol.149. 997-1007 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Nagura H,Kimura N.: Essentials of Mucosal Immunology. Academic Press, 598 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 笹野 公伸, 名倉 宏: "Analysis of cell damage and proliferation in Helicobacter pylori-infected human gastric mucosa from patients with gastric adenocarcinoma" Am.J.Pathol.151. 821-829 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 木村 伯子, 名倉 宏: "Plasma chromograin A in pheochromocyatma,catecholamine,parathyroid hormone and pituitary hormones." Endocr.J.44. 319-327 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 大谷 明夫, 名倉 宏: "Expression of costimulatory molecules B7-1 and B7-2 in macrophages and granulomas of Crohn's disease : Demonstration of cell to cell contact with T lymphocytes." Lab.Invest.77. 175-184 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 笹野 公伸, 名倉 宏: "Ultrastructural and confocal lase scanning microscopiod examination of TUNEL positive cells." J.Pathol.181. 235-242 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 笹野 公伸, 名倉 宏: "Colocalization of ll beta-hydroxysteroid dehydrogenase type II and mineralocorticoid receptor in human epithelia." J.Clin.Endocr.Matabol.82. 3859-3863 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sasano, H., Nagura, H., et al: "In situ analysis of tissue dynamics and p53 expression in human gastric mucosa." Journal of Pathology. 179. 39-42 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohtani, H., Nagura, H., et al: "Immunophenotypic characterization of Epstein-Barr virus-associated gastric carcinoma : Massive infiltration by proliferating CD8^+ T-lymphocyte." Laboratory Investigation. 75. 67-76 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sasano, H., Nagura, H., et al: "Immunohistochemical study DNA topoisomerase II in human gastric disorders." American Journal Pathology. 149. 997-1007 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kumura, N., Sasano, H., Nagura, H., et al: "Expression of prohormone convertase, PC2, in adrenocorticotropin-producing thymic carcinoid with elevated plasma corticotropin-relasing homone." Journal of Clinical Endocrinology and Metabolism. 81. 390-395 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Ohtani, H., Nagura, H., et al: "Dual over-expression pattern on membrane-type metalloproteinase-1 in cancer and stromal cells in human gastrointestinal carcinoma revealed by in sity hybridization and immunoelectron microscopy." International Journal of Csncer. 68. 565-570 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kimura, N., Nagura, H., et al: "Plasma chromogranin A in prostatic carcinoma and neuroendocrine tumors." The Journal of Urology. 157. 565-568 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Nagura, H., Kimura, N., et al: "Essentials of Mucosal Immunology (分担)" Academic Press, 597 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 太田達郎 他: "Henoch-Schonlein紫斑病における消化管病変の免疫組織化学的研究" 消化管と免疫. 31. 101-110 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Sasano Hironobu rt al.: "4d4BP in the human adrenal cortex in its disorders." J Clin Endocrinol Metab. 80. 2378-2380 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kimura Noriko et al.: "Immunohistochemical localization of chromostatin and pancreastatin,chromogranin A-derived bioactive peptides,in normal and neoplastic neuroendocrine tissues." Endocrine Pathology. 6. 35-43 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takayuki Mizoi et al.: "Intercellular adhesion molecule-l expression by macrophages in human gastrointestinal carcinoma:Possible roles as hoes immune/inflammatory reaction." Pathology International. 45. 565-572 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Ohtani Haruo et al.: "Similarities of in situ mRNA expression between gelatinase A (MMP-2)and type I procollagen in human gastrointestinal carcinoma:Comparison with granulation tissue reaction." Jpn J Cancer Res. 86. 833-839 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kimura Noriko et al.: "Expression of prohormone convertase,PC2,in adrenocorticotropin-producing thymic carcinoid with elevated plasma corticotropin-releasing hormone." J Clin Endocrinol Metab. 81. 390-395 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] 名倉 宏: "現代病理学体系(1)(分担)" 中山書店, 311 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nagura Hiroshi: "Essentials of Mucosal Immunology(分担)" Academic Press(in press), (1996)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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