Regulation of Intestinal Mucosal Immunity in a Mouse Model on Inflammatory Bowel Disease

• Project/Area Number: 16591311
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Osaka University
• Principal Investigator: ITO Toshinori Osaka University, Graduate School of Medicine, Endowed Chair Professor, 医学系研究科, 寄附講座教授 (20231152)
• Co-Investigator(Kenkyū-buntansha): SHIMIZU Shigemi Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (70271020) ; KIYONO Hiroshi Tokyo University, Graduate School of Medicine, Professor, 医学研究科, 教授 (10271032)
• Project Period (FY): 2004 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2005: ¥1,600,000 (Direct Cost: ¥1,600,000); Fiscal Year 2004: ¥1,900,000 (Direct Cost: ¥1,900,000)
• Keywords: Inflammatory Bowel Disease / IL-10 knock out mouse / Bcl transgenic mouse / Intestinal epithelium / apoptosis / Th1 / IL-10^<- / ->マウス / 消化管上皮

Research Abstract

Interleukin-10 gene-deficient (IL-10^<-/->) mice spontaneously develop an intestinal inflammation characterized by multifocal lesions throughout the gastrointestinal tract, which has many similarities to human Crohn's disease. In our current study of this model we have elucidated the role of apoptosis in intestinal epithelial cells in the onset and development of the colonic inflammation. We have employed human Bcl-2 transgenic mice, in which human Bcl-2, an anti-apoptosis protein, was expressed in epithelial cells but not intestinal lymphocytes, on an IL-10^<-/-> null background. In comparison with the non-transgenic IL-10% mice, the Bcl-2 transgenic mice had less apoptosis of the intestinal epithelium, better-maintained mucosal barrier, and less intestinal inflammation. Bcl-2 did not alter the cytokine production profile of infiltrating intestinal lymphocytes, but it reduced the number of the cells, probably resulting in diminished inflammation. These results imply that epithelial cell apoptosis is an important component of disorders of chronic intestinal inflammation. Measures to limit the apoptosis might be considered for preventing or treating such conditions.

Research Products

• [Journal Article] Therapeutic effects of roxithromycin in Interleukin-10-deficient colitis. (2007)
  • Author(s): H.Tamagawa, T.Hiroi, T.Mizushima, T.Ito, H.Matsuda, H.Kiyono
  • Journal Title: Inflamm Bowel Dis (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A novel sphingosine 1-phosphate receptor agonist, KRP-203, regulates chronic colitis in IL-10 gene-deficient mice (2007)
  • Author(s): J.Song, C.Matsuda, Y.Kai, T.Nishida, T.Mizushima, K.Nakajima, M.Kinoshita, T.Yasue, Yoshiki Sawa, T.Ito
  • Journal Title: J Pharmacol Exp Ther (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Therapeutic effect of a new immunosuppressive agent, everolimus on interleukin-10 gene-deficient mice with colitis. (2007)
  • Author(s): C.Matsuda, T.Ito, J.Song, T.Mizushima, T.Tamagawa, Y Kai, Y.Hamanaka, M.Inoue, T.Nishida, H.Matsuda, Y.Sawa
  • Journal Title: Clin Exp Immunol (In press)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Therapeutic effects of roxithromycin in Interleukin-10-deficient colitis (2007)
  • Author(s): H.Tamagawa, T.Hiroi, T.Mizushima, T.Ito, H.Matsuda, H.Kiyono
  • Journal Title: Inflamm Bowel Dis (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A novel sphingosine 1-phosphate receptor agonist, KRP-203, regulates chronic colitis in IL-10 gene-deficient mice (2007)
  • Author(s): J.Song, C.Matsuda, Y.Kai, T.Nishida, T.Mizushima, K.Nakajima, M.Kinoshita, T.Yasue, Yoshiki Sawa, T.Ito
  • Journal Title: J Pharmacol Exp Ther (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Therapeutic effect of a new immunosuppressive agent, everolimus on interleukin-10 gene-deficient mice with colitis. (2007)
  • Author(s): C.Matsuda, T.Ito, J.Song, T.Mizushima, T.Tamagawa, Y Kai, Y.Hamanaka, M.Inoue, T.Nishida, H.Matsuda, Y.Sawa.
  • Journal Title: Clin Exp Immunol (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Colitis in Mice Lacking the Common Cytokine Receptor γ Chain Is Mediated by IL-6-Producing CD4+T cells (2005)
  • Author(s): Y.Kai, I.Takahashi, H.Ishikawa, T.Hiroi, T.Mizushima, C.Matsuda, D.Kishi, H.Hamada, H.Tamagawa, T.Ito, et al.
  • Journal Title: Gastroenterology 128 Pages: 922-934
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Colitis in Mice Lacking the Common Cytokine Receptor y Chain Is Mediated by IL-6-Producing CD4+T cells (2005)
  • Author(s): Y.Kai, I.Takahashi, H.Ishikawa, T.Hiroi, T.Mizushima, C.Matsuda, D.Kishi, H.Hamada, H.Tamagawa, T.Ito, et al.
  • Journal Title: Gastroenterology 128 Pages: 922-934
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Therapeutic Effects of a New Lymphocyte Homing Reagent FTY720 in Interleukin-10 Gene-deficient Mice with Colitis (2004)
  • Author(s): Tsunekazu Mizushima
  • Journal Title: Inflamm Bowel Dis 10-3 Pages: 182-192