2002 Fiscal Year Final Research Report Summary
Study of mucosal immune response in the murine model of inflammatory bowel disease -Therapeutic effect of a new immunosuppressive reagent FTY720-
| Project/Area Number |
13671301
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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 | Osaka University |
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Principal Investigator |
ITO Toshinori Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (20231152)
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| Co-Investigator(Kenkyū-buntansha) |
KIYONO Hiroshi The Institute of Medical Science The University of Tokyo, Professor, 医科学研究所, 教授 (10271032)
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| Project Period (FY) |
2001 – 2002
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| Keywords | inflammatory bowel disease / Interleukin-10 gene-deficient mice / FTY720 / Colonic lamina propria lymphocyte / Peyer's patch / Mesenteric lymph node / Lamina propria |
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| Research Abstract |
Background & Aims: FTY72O is a novel lymphocyte homing agent that possesses potent immunosuppressive activity. The immunosuppression induced by FTY72O is mediated by completely different mechanisms from those of conventional immunosuppressants, i.e., by accelerated lymphocyte homing. Interleukin-10 gene- deficient (IL-10^<-/->) mice spontaneously develop an enterocolitis by 2-3 months of age that has many histologic similarities to human Crohn' sdisease. In this study, we examined the efficacy of FTY72O in the treatmentof chronic colitis in an IL-10 ^<-/-> mouse model.
Methods: FTY72O was administered orally at a dose of 0.3 mg/kg/day for 4 weeks to 16-20-wk-old IL-10^<-/-> mice with clinical signs of colitis. The gross and histologic appearance of the colon, the numbers and phenotype of lamina propria lymphocytes, and cytokine production by the lymphocytes were compared with those characteristics in a control group.
Results: Single-dose administration of FTY72O resulted in the sequestration of circulating lymphocytes within Peyer's patches and mesenteric lymph nodes, with a corresponding reduction in the numbers of lymphocytes in the peripheral blood. Four- week administration resulted in a significant decrease in the severity of colitis, accompanied by a significant reductionin the CD^<4+> lymphocyte subpopulation in the colonic lamina propria and in IFN-γ production by the colonic lymphocytes.
Conclusions: FTY720, a novel lymphocyte homing agent, treatment of adult mice resulted in amelioration of established chronic colitis in IL-10^<-/->mice that have many similarities to human Crohn's disease.
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[Publications] Inoue Y, Noro H, Komoda H, Kimura T, Mizushima T, Taniguchi E, Yumiba T, Itoh T, Ohashi S, Matsuda H.: "Related Articles, Links Completely laparoscopic total colectomy for chronic constipation : report of a case"Surg Today. 32(6). 551-554 (2002)
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「研究成果報告書概要(和文)」より
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[Publications] Okuda Y, Takahashi I, Kim JK, Ohta N, Iwatani K, Iijima H, Kai Y, Tamagawa H, Hiroi T, Kweon MN, Kawano S, Takeda K, Akira S, Sasaki Y, Hori M, Kiyono H.: "Related Articles Links Development of colitis in signal transducers and activators of transcription 6 -deficient T-cell receptor alpha -deficient mice : a potential role of signal transducers and activators of transcription 6 -independent interleukin -4 signaling for the generation of Th2 -biased pathological CD4+ betabetaT cells"Am J Pathol. Jan;162(1). 263-271 (2003)
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「研究成果報告書概要(和文)」より
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[Publications] Okuda Y, Takahashi I, Kim JK, Ohta N, Iwatani K, Iijima H, Kai Y, Tamagawa H, Hiroi T, Kweon MN, Kawano S, Takeda K, Akira S, Sasaki Y, Hori M, Kiyono H.: "Development of colitis in signal transducers and activators of transcription 6-deficient T-cell receptor alpha-deficient mice: a potential role of signal transducers and activators of transcription 6-independent interleukin-4 signaling for the generation of Th2-biased pathological CD4+ betabetaT cells"Am J Pathol.. 162(1). 263-271 (2003)
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「研究成果報告書概要(欧文)」より
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[Publications] Yanagita M, Shimabukuro Y, Nozaki T, Yoshimura N, Watanabe J, Koide H, Terakura M, Saho T, Takedachi M, Jang MH, Kiyono H, Murakami S.: "IL-15 up-regulates iNOS expression and NO production by gingival epithelial cells"Biochem Biophys Res Commun.. 297(2). 329-334 (2002)
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「研究成果報告書概要(欧文)」より
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