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1998 Fiscal Year Final Research Report Summary

Interaction of mucosal immune cells, stromal cells, and microvascular endothelial cells in inflammatory bowel disease

Research Project

Project/Area Number 09670538
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionNAGOYA UNIVERSITY

Principal Investigator

KUSUGAMI Kazuo  SCHOOL OF MEDICINE,NAGOYA UNIVERSITY SENIOR LECTURER, 医学部, 講師 (00234427)

Co-Investigator(Kenkyū-buntansha) SHINODA Masataka  SCHOOL OF MEDICINE,STAFF, 医学部, 医員
ANDO Takafumi  SCHOOL OF MEDICINE,STAFF, 医学部, 医員
INA Kenji  SCHOOL OF MEDICINE,STAFF, 医学部, 医員
Project Period (FY) 1997 – 1998
Keywordsulcerative colitis / Crohn's disease / interleukin-15 / interleukin-8 / lamina propria mononuclear cells / polymorphonuclear neutrophils
Research Abstract

An infiltration of immune and inflammatory cells, such as macrophages, T-cells, and B-cells, in the affected intestine makes the main pathological features of inflammatory bowel disease (IBD). Recruitment and activation of immune cells may be accelerated by release of immunoregulatory and chemotactic cytokines. The levels of immunoregulatory cytokines, such as interleukin(IL)-2 have been the subject of conflicting reports, probably because of consistently lower activity in the intestinal mucosa. Recently IL-7 and IL-15, which utilize common gamma-chains of IL-2 receptor, have been reported to exert many of the immunological activities on immune cells previously described for IL-2. Therefore, we examined the concentrations of IL-15, IL-7, and IL-2 in the organ cultures of intestinal mucosal tissues obtained from controls and patients with ulcerative colitis or Crohn's disease. IL-7 activity was detected only in 6 of total 100 cultures and IL-2 activity was totally absent in cultures of … More all patients group. In contrast, measurable levels of IL-15 were detected in all organ cultures with higher concentrations in IBD.In situ hybridization showed a localization of IL-15 messenger RNA to epithelial cells and infiltrating mononuclear cells, in which the signal was observed more diffusely in IBD specimens. Functionally, recombinant (r)IL-15 induced a dose-dependent increase in proliferative response and lymphokine activated-killer cell activity in both IBD and control lamina propria mononuclear cells (LPMC). Even more, rIL-15 was capable of inducing TNF-alpha and IFN-gamma production in LPMC, thus suggesting that IL-15 is an important cytokine in immune activation of mucosal immune cells in the intestinal mucosa with IBD.
Tissue accumulation of polymorphonuclear neutrophils (PMN) is another characteristic feature in the mucosal lesion of IBD.Increased mucosal production of IL-8 was observed in patients with IBD.Elevated levels of IL-8 may be involved in migration of PMN from the vascular space into the affected intestine and adhesion to the extracellular matrix. Moreover, mucosal specimens obtained from IBD patients exhibited higher levels of granulocyte colony-stimulating factor activity, thus providing possible mechanisms for tissues accumulation of PMN in IBD through inhibition of their apoptotic process. Less

  • Research Products

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Tetsu Sakai: "Fasmediated cytotoxicity by intestinal intraepithelial lymphocytes during acute graet-versus-host disease in mice." Gastroenterology. 113. 168-174 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kenji Ina: "Mucosal interleukin-8 is involeved in neutrophil migration and binding to extracellular matrix in inflammatory bowel disease." American Journal of Gastroenterology. 92. 1342-1346 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] David G Binion: "Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease." Gastroenterology. 112. 1895-1907 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tetsu Sakai: "Interleukin 15 activity in the rectal mucosa of inflammatory bowel disease." Gastroenterology. 114. 1237-1243 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kenji Ina: "Increased mucosal production of granulocyte colony-stimulating factor is related to a delay in neutrophil apoptosis in inflammatory bowel disease." Journal of Gastroenterology and Hepatology. 14. 46-53 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tetsu Sakai, Yuki Kimura, Kazuo Kusugami, et al.: "Fas-mediated cytotoxicity by intestinal intraepithelial lymphocytes during acute graft-vs.-host disease in mice." Gastroenterology. 113. 168-174 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kenji Ina, Kazuo Kusugami, Takeo Yamaguchi, et al.: "Mucosal interleukin-8 is involved in neutrophil migration and binding to extracellular matrix in inflammatory bowel disease." American Journal of Gastroenterology. 92. 1342-1346 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] David G Binion, Gail West, Kenji Ina, et al.: "Enhanced leukocyte binding by intestinal microvascular endothelial cells in inflammatory bowel disease." Gastroenterology. 112. 1895-1907 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tetsu Sakai, Kazuo Kusugami, Hitoshi Nishimura, et al.: "Interleukin-15 activity in the rectal mucosa of inflammatory bowel disease." Gastroenterology. 114. 1237-1243 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kenji Ina, Kazuo Kusugami, Yuji Nishio, et al.: "Increased mucosal production of granulocyte colony-stimulating factor is related to a delay in neutrophil apoptosis in inflammatory bowel disease." Journal of Gastroenterology and Hepatology.14. 46-53 (1999)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 1999-12-08  

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