Clarify the mechanisms of Interleukin-13 induces tissue damage with modification of cell-cell adhesion in the intestinal epithelial cells

• Project/Area Number: 19790505
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Research Institute, International Medical Center of Japan
• Principal Investigator: KAWASHIMA Rei Research Institute, International Medical Center of Japan, 研究員 (70392389)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥3,610,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥510,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2007: ¥1,400,000 (Direct Cost: ¥1,400,000)
• Keywords: 消化器学(食道、胃、小腸、大腸) / IL-13 / IL-4 / 消化管上皮細胞 / 消化器学 / サイトカイン

Research Abstract

腸管一次培養法やヒト大腸癌細胞株を用いた実験により、IL-13はbeta-cateninやZO-1などの膜染色性を弱めることから、IL-13は細胞間接着を破壊するような細胞傷害作用を持つ。TUNEL法を用いて、アポトーシスの誘導について解析したところ、IL-4は上皮細胞にアポトーシスを誘導しないが、IL-13はTNF-αに匹敵する数の細胞にアポトーシスを誘導することが明らかとなった。
IL-13が腸管上皮細胞に対して直接的に細胞間結合分子の作用減弱を伴う傷害作用を誘導することが証明され、消化管におけるIL-13の組織傷害メカニズムを解明する上で重要な知見を得られた。

Research Products

• [Journal Article] TWEAK/Fn14 Pathway : a nonredundant role in intestinal damage in mice through a TWEAK/intestinal epithelial cell axis (2009)
  • Author(s): T. Dohi
  • Journal Title: Gastroenterology 136 Pages: 912-923
  • Peer Reviewed
• [Journal Article] DNA hypermethylation contributes to incomplete synthesis of carbohydrate determinants in gastrointestinal cancer. (2008)
  • Author(s): Kawamura YI, Toyota M, Kawashima R, Hagiwara T, Suzuki H, Imai K, Shinomura Y, Tokino T, Kannagi R, Dohi T
  • Journal Title: Gastroenterology 135(1) Pages: 142-151
• [Journal Article] Dose-dependent differential regulation of cytokine secretion from macrophages by fractalkine. (2007)
  • Author(s): Mizutani N, Sakurai T, Shibata T, Uchida K, Fujita J, Kawashima R, Kawamura YI, Toyama-Sorimachi N, Imai T, Dohi T
  • Journal Title: J Immunol. 179(11) Pages: 7478-87
• [Journal Article] Dose-dependent differential regulation of cytokine secretion from macrophages by fractalkine. (2007)
  • Author(s): Noriko Mizutani, et. al.
  • Journal Title: J.Immunol 179(11) Pages: 7478-7487
  • Peer Reviewed
• [Presentation] IL-13 disrupts tight junction in the intestinal epithelial cells by modulating expression of ZO-1, occludin and claudin-2 (2008)
  • Author(s): Rei Kawashima, et al
  • Organizer: 日本免疫学会学
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] IL-13 disrupts tight junction in the intestinal epithelial cells by modulating expression of ZO-1, occludin and claudin-2 (2008)
  • Author(s): Kawashima R
  • Organizer: 第38回日本免疫学会学術集会
  • Place of Presentation: 京都
  • Year and Date: 2008-12-02
• [Presentation] Interleukin-13 Induces Tissue Damage with Relocation of β-Catenin and Modification of Cell-Cell (2008)
  • Author(s): Rei Kawashima, et al
  • Organizer: Adhesion in the Epithelial Cells Digestive Disease Week 2008
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2008-05-18
• [Presentation] Interleukin-13 Induces Tissue Damage with Relocation of β-Catenin and Modification of Cell-Cell Adhesion in the Epithelial Cells (2008)
  • Author(s): Kawashima R
  • Organizer: Digestive Disease Week 2008
  • Place of Presentation: San Diego, U.S.A.
  • Year and Date: 2008-05-18
• [Presentation] IL-13 disrupts the cell-cell adhesion of intestinal epithelial cells (2007)
  • Author(s): Rei Kawashima, et al
  • Organizer: 日本免疫学会
  • Place of Presentation: 品川
  • Year and Date: 2007-11-21
• [Presentation] Two distinct types of aberrant responses in the colonic lamina propria cells to lipopolysaccharide (LPS) in ulcerative colitis (2007)
  • Author(s): Rei Kawashima, et al
  • Organizer: 13th International Congress of Mucosal Immunology
  • Place of Presentation: 東京
  • Year and Date: 2007-07-11
• [Presentation] Two distinct types of aberrant responses in the colonic lamina propria cells to lipopolysaccharide(LPS)in ulberative colitis (2007)
  • Author(s): Rei Kawashima, et. al.
  • Organizer: 13th International Congress of Mucosal Immunology
  • Place of Presentation: 東京
  • Year and Date: 2007-07-11
• [Presentation] Aberrant responses of human colonic macrophage-type cells to lipopolysaccharide in ulcerative colitis: upregulated expression of MD-2 and production of Inflammatory cytokines (2007)
  • Author(s): Rei Kawashima, et al
  • Organizer: Digestive Disease Week2007
  • Place of Presentation: Washington D. C
  • Year and Date: 2007-05-22
• [Presentation] Aberrant responses of human colonic macrophage-type cells to lipopolysaccharide in ulcerative colitis: upregulated expression of MD-2 and roduction of Inflammatory cytokines (2007)
  • Author(s): Rei Kawashima, et. al.
  • Organizer: Digestive Disease Week 2007
  • Place of Presentation: Washington D. C
  • Year and Date: 2007-05-22