Study of molecular pathology for intestinal stasis-associated bowel diseases
| Project/Area Number |
11671230
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Nagoya University |
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Principal Investigator |
UESAKA Katsuhiko School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (20283434)
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| Co-Investigator(Kenkyū-buntansha) |
NAGINO Masato School of Medicine, Nagoya University, Associate Professor, 医学部, 講師 (20237564)
KAMIYA Jyunichi School of Medicine, Nagoya University, Associate Professor, 医学部, 講師 (70194975)
NIMURA Yuji School of Medicine, Nagoya University, Professor, 医学部, 教授 (80126888)
ODA Kouji School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (30311715)
YUASA Norihiro School of Medicine, Nagoya University, Research Associate, 医学部, 助手 (00303610)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | intestinal stasis / enteric microflora / indigenous gastrointestinal microflora / inflammation / adhesion molecules / ICAM-1 / endothelium |
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| Research Abstract |
Study 1 Influence of the enteric microflora on endothelial cell adhesion molecule expression was investigated using germ-free mice. Constitutive intercellular adhesion molecule-1 (ICAM-1) was significantly lower in the gastrointestinal tract, liver, pancreas, skeletal muscle, and skin of germ-free mice compared with their conventional counterparts. Intragastric inoculation of germ-free mice with cecal microflora from conventional mice restored ICAM-1 expression to normal values. ICAM-1 expression in the lung, heart, and brain did not differ between the two groups of mice. These findings indicate that the indigenous gastrointestinal microflora are responsible for a significant fraction of endothelial ICAM-1 expression.
Study 2 Mechanisms how the enteric microflora affect endothelial cell ICAM-1 expression was studied using transgenic mice. In control mice, ICAM-1 expression in the distal colon was significantly lower than that in the cecum. The difference in ICAM-1 expression between the
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two organs was reduced in either CD11/CD18 or P-selectin knock-out mice. These findings suggest that some components of blood cells recruited into the intestinal tissue may contribute to the enhanced ICAM-1 expression in the murine cecum.
Study 3 To clarify the role of blind pouch, such as the appendix and cecum, in the development of ulcerative colitis, following study was done. While constitutive ICAM-1 expression was significantly higher in the cecum than in the distal colon of wild type mice, ICAM-1 expression in the cecum of germfree counterparts was comparable to that in their distal colon. The magnitude of the difference in ICAM-1 expression between the cecum and the distal colon was significantly reduced in the germfree animals, compared to that in the germ replete wild types. This abolished difference between the two organs of germfree mice was restored following reestablishment of the enteric microflora. These results indicate that the normal enteric microflora contributes to the higher expression of ICAM-1 in the murine cecum. Less
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Report
(3 results)
Research Products
(8 results)
