| Project/Area Number |
04454178
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Human pathology
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| Research Institution | TOHOKU UNIVERSITY |
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Principal Investigator |
NAGURA Hiroshi Tohoku Univ. - Dept.Pathol., Professor, 医学部, 教授 (90022821)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Iwao Tohoku Univ. - Dept.Surgery, Associate Professor, 医学部, 助教授 (60125557)
SASANO Hironobu Tohoku Univ. - Dept.Pathol., Research Associate, 医学部, 助手 (50187142)
OHTANI Haruo Tohoku Univ. - Dept.Pathol., Research Associate, 医学部, 助手 (30133987)
KIMURA Noriko Tohoku Univ. - Dept.Pathol., Associate Professor, 医学部, 助教授 (80142975)
MASUDA Takayuki Tohoku Univ. - Bull, Coll, Med.Sci., Professor, 医療短期大学部, 教授 (00113910)
樋渡 信夫 東北大学, 医学部, 講師 (00133950)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 1993: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1992: ¥3,900,000 (Direct Cost: ¥3,900,000)
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| Keywords | Inflammatory bowed disease / Mucosal immunity / Gut hormone / Vasoactive intestinal peptide / VIP receptor / Immunohistochemistry / Cell adhesion molecule / Neonate / in situ hypridization / ニューロペプチド / VIP / サブスタンスP / エンドセリン / 潰瘍性大腸炎 |
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| Research Abstract |
There is a great deal of evidence for the neurohormonal influence on vasious aspects of the immuno-inflammatory response of the gastrointestinal mucosa. The intestine contains highly specialized subdivision of both the neuroendocrine and immune systems, and the mucosal surface is specially well designed to allow for interactions between nerves and the cells of the immune system. The intestinal mucosa contains significant amount of the neuropeptide, neurotransmitters, such as vasoactive intestinal peptide (VIP), substance P (SP) and somatostatin (SOM), which have been shown to regulate the function of immune effector cells including gut-associated lymphoid tissue (GALT) in the intestinal mucosa.
In normal intestinal mucosa neuropeptide-containing nerves are intimately correlated to glands, blood vessels, and immune effector cells, VIP and SP are solely present in nerves, and mRNA for VIP found in a part of endocrine cells and macrophages. In hypervascular areas with active inflammation i
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n the ulcerative colitis (UC) mucosa, increasing innervation of VIP- and SP- nerves are observed along the proliferated and dilated venule-like blood vessels, which strongly express several cell adhesion molecules including ICAM-1(CD54) and E-selectin. These nerves around crypt abscess were almost absent. These distribution abnormalities of neuropeptide-containing nerves may disturb the immuno-inflammatory regulation in the UC mucosa, and cause the mucosal damage.
Neuropeptide recepters on immunocytes in the intestinal mucosa have added further evidence to the notion that functional interaction between nerves and mucosal immune system can exist. Lymphocytes of both B- and T-cell lineages can express neuropeptide recepter, and dendritic cells of the germinal center of Peyer's patches (FDC) and macrophages in the lamina propria also carry these receptors, which are absent in FDC of neonates before the mucosal immune system matures.
Abnormalities and immaturity in the neuroendocrine-immune interactions may be important in the desease pathogenesis in immuno-inflammatory disorders in the intestine, and cause the mucosal damage and prolonged inflammation. Psychological stress can influence the symptoms of inflammatory bowel disease through the neuroendocrine-immune interrelationship. Less
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