2004 Fiscal Year Final Research Report Summary
Role of intestinal epithelial tight junction permeability in inflammatory bowel disease
| Project/Area Number |
13670576
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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 |
Gastroenterology
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| Research Institution | Fukuoka University |
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Principal Investigator |
AOYAGI Kunihiko Fukuoka Univ., Hospital, Lecturer, 病院, 講師 (00253435)
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| Co-Investigator(Kenkyū-buntansha) |
SAKISAKA Shotaro Fukuoka Univ., Sch.Med., Professor, 医学部, 教授 (90158923)
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| Project Period (FY) |
2001 – 2004
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| Keywords | Inflammatory bowel disease / Tight junction |
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| Research Abstract |
It is well known that intestinal permeability is increased in inflammatory bowel diseas(IBD including Crohn's disease and ulcerative colitis.
Various intraluminal substances such as endotoxin and other toxins stimulate mucosal inflammatory cells when they pass through the epithelial barrier. Although intestinal permeability is considered to be important in the pathogenesis of IBD, there remains to be unclear. In our study, tight junction(TJ) barrier function was evaluated using monolayer cell cultures (T84) and rat models (5% dextran sulfate sodium-induced colitis).E ffects of antiinflammatory drugs (ecabet sodium and 5-aminosalicylates) were also identified. The structure and localization of TJ protein and intestinal permeability were determined by immunohistochemistry and transepithelial electric resistance(TER) or extravasation of Evans blue dye, respectively.
In cell culture, interferon gamma disrupted the TJ structure and decreased TER, but ecabet sodium recovered them. In DDS colitis, length of the colon, tissue myeloperoxidase activity, histological inflammation score, permeability were increased, and immunohistochemical localization of TJ protein showed a decreased staining, but 5-aminosalicylates administration ameliorated their changes. These results suggest that drugs for IBD improve the disruption of TJ, leading to act, in part, as an anti-inflammatory property. A new clinical approach targeting intestinal tight junction may be promising in IBD.
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