2004 Fiscal Year Final Research Report Summary
Development of novel mouse model of human Crohn's disease
| Project/Area Number |
15590684
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Keio University |
|---|
Principal Investigator |
INOUE Nagamu Keio University, Department of Medicine, Instructor, 医学部, 助手 (00232546)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HIBI Toshifumi Keio University, Department of Medicine, Professor, 医学部, 教授 (50129623)
ISHIKAWA Hiromichi Keio University, Department of Medicine, Professor, 医学部, 教授 (20051667)
YAJIMA Tomoharu Keio University, Department of Medicine, Instructor, 医学部, 所長 (70306710)
NOMURA Tatsuji Central Laboratories for Experimental Animals, Director, 所長 (10072399)
|
|---|
| Project Period (FY) |
2003 – 2004
|
| Keywords | Crohn's disease / NOG mice / intestinal microflora / disease model mice / inflammatory bowel disease / stem cell |
|---|
| Research Abstract |
Inflammatory bowel disease(IBD) is a chronic inflammation of the gastrointestinal tract and its prevalence has been increasing in Japan. However, no fundamental therapy has been established because the etiology of IBD remains obscure in spite of extensive pathophysiological researches. Recent advances in the understanding of the pathophysiological conditions of IBD have provided new immune system modulators as therapeutic tools. Animal models, such as dextran sulfate sodium(DSS)-indeced colitis, interleukin-10 deficient(IL-10-/-) mice and CD4^+CD45^<RBhigh> transfer model, have been widely used for studying the intestinal inflammation and testing therapeutic effect of newly-developed drugs. However, there has not been established ideal animal models resembling the pathogenesis of human IBD including intestinal microflora which plays an important role for inducing and perpetuating the intestinal inflammation.
At First, we crossed NOD-SCID mice with IL-2Rγc knock out mice and obtained NOD/SCID×IL-2RγcKO(NOG) mice which completely deficient immnocompetent cells and is ideal for the recipient of transplant experiment. We already established stable supply of the NOG mice for the present study.
Next, we studied the importance of intestinal microfolora in the intestinal inflammation using human flora associated(HFA) mice. Results of flora analysis indicated that derangement of intestinal flora with ulcerative colitis(UC) was reproduced in HFA mice model. However, intestinal inflammation was not induced by administration of UC flora in wild-type mice. In contrast, mice colonized with UC flora presented severe inflammation compared with mice colonized with healthy control(HC) flora upon DSS administration. Moreover, in IL-10-/- mice, several inflammatory parameters were also severer in UC flora mice than those in HC flora mice. These results suggested that breakdown of intestinal bacterial balance increased the susceptibility of intestinal inflammatory stimuli.
|
Research Products
(12 results)
-
-
[Journal Article] Non-pathogenic Escherichia coli strain Nissle 1917 prevents murine acute and chronic colitis.2005
Author(s)
Kamada N, Jnoue N, Hisamatsu T, Okamoto S, Matsuoka K, Sato T, Chinen H, Hong KS, Yamada T, Suzuki Y, Suzuki T, Watanabe N, Tsuchimoto K, Hibi T
-
Journal Title
Inflamm Bowel Dis (in press)
Description
「研究成果報告書概要(欧文)」より
-
-
-
-
[Journal Article] T-bet up-regulation and subsequent interleukin 12 stimulation are essential for the induction of Th1 mediated immunopathology in Crohn's disease.2004
Author(s)
Matsuoka K, Inoue N, Sato T, Okamoto S, Hisamatsu T, Kishi Y, Sakuraba A, Hitotsumatsu O, Fukushima T, Kanai T, Watanabe M, Ishii H, Hibi T
-
Journal Title
Gut 53(9)
Pages: 1303-1308
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Human intestinal epithelial cell-derived interleukin(IL)-18, along with IL-2, IL-7 and IL-15, is a potent synergistic factor for the proliferation of intraepithelial lymphocytes.2004
Author(s)
Okazawa A, Kanai T, Nakamaru K, Sato T, Jnoue N, Ogata H, Iwao Y, Ikeda M, Kawamura T, Makita S, Uraushihara K, Okamoto H, Yamazaki M, Kurimoto M, Ishii H, Watanabe M, Hibi T
-
Journal Title
Clin Exp Immunol 136(2)
Pages: 269-276
Description
「研究成果報告書概要(欧文)」より
-
[Journal Article] Hyperexpression of inducible costimulator and its contribution on lamina propria T cells in inflammatory bowel disease.2004
Author(s)
Sato T, Kanai T, Watanabe M, Sakuraba A, Okamoto 5, Nakai T, Okazawa A, Inoue N, Totsuka T, Yamazaki M, Kxoczek RA, Fukushima T, Ishii H, Hibi T
-
Journal Title
Gastroenterology 126(3)
Pages: 829-839
Description
「研究成果報告書概要(欧文)」より
-
-
-
[Journal Article] Contrasting action of IL-12 and IL-18 in the development of dextran sodium sulfate colitis in mice.2003
Author(s)
Takagi T, Kanai T, Okazawa A, Sato T, Takaishi H, Inoue N, Ogata H, Hoshino K, Takeda K, Akira S, Watanabe M, Ishii H, Hibi T
-
Journal Title
Scand J Gastroenterol 38(8)
Pages: 837-844
Description
「研究成果報告書概要(欧文)」より
-
