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Invention of the new treatment for inflammatory bowel diseases using antiCD30 monoclonal antibody

Research Project

Project/Area Number 18590689
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKyushu University

Principal Investigator

MUTA Hiromi  Kyushu University, Department of Medicine and Bioregulatory Science, Guest Associate Professor (40325478)

Co-Investigator(Kenkyū-buntansha) TANI Kenzaburo  Kyushyu Univ., Medical Institute of Bioregulation, Professor (00183864)
KURITA Ryo  Kyushyu Univ., Medical Institute of Bioregulation, Assistant Professor (90380526)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsCD30 / antibody therapy / inflammatory bowel disease / mice model of enteritis / knock out mice
Research Abstract

Background and Aims: Although CD30 has long been recognized as an important marker on many lymphomas of diverse origin and as activation molecule on B and T cells, its primary function has remained obscure. A soluble form of CD30 (sCD30) is detectable in serum as a consequence of shedding of CD30 in some disease conditions. This study investigates the role of CD30L/CD30 signals in intestinal mucosal damage.
Methods: Levels of sCD30 in sera obtained from Ulcerative colitis (UC) and Crohn's disease (CD) patients and healthy donors were assessed. CD30 expression was determined by immunohistochemistry. An enteritis models of mice, induced by anti-CD3 was studied in wild type (WT) BALB/c mice and in CD30L knockout mice in the BALB/c background (CD30LKO).
Results: Increased levels of sCD30 were observed in both UC and CD patients. The levels of sCD30 were correlated with the disease activity both in UC and CD. CD30 positive cells were observed at the inflammation site of UC and CD. In murine models of enteritis, histological intestinal damage were significantly reduced in CD30LKO mice and associated with differences in cytokine levels. Moreover, blocking of CD30/CD30L by CD30Ig signals resulted reduction of inflammation.
Conclusions: Detection of CD30 expressing cells at the inflammation site and association of increased sCD30 levels with disease activity suggest that CD30/CD30L signals play an important role in disease pathogenesis of UC and CD. CD30 acts as an accelerator of enteritis in murine diease models. Successful blockade of enteritis by CD30Ig suggests a potential tool for future therapy for these diseases.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (4 results)

All 2006

All Presentation (4 results)

  • [Presentation] CD30/CD30 ligand シグナルの炎症性腸疾患における役割の検討2006

    • Author(s)
      杣田 真一、牟国 浩実、谷憲 三朗, 他
    • Organizer
      第48回日本消化器病学会大会
    • Place of Presentation
      札幌
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of CD30 in the inflammatory intestine2006

    • Author(s)
      Shiniclu Somada, Hiromi Muta, Kenzaburo Tarsi, et. al.
    • Organizer
      DDW 2006
    • Place of Presentation
      Los Angeles,USA
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Expression of CD30 in the inflammatory intestine2006

    • Author(s)
      Shinichi, Somada, Hiromi, Muta, Kazuhiko, Nakamura, R, Podack, Eckhard, Kuniomi, Honda, Hajime, Nawata, Kenzaburo, Tani
    • Organizer
      DDW 2006
    • Place of Presentation
      Los Angeles USA
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] The role of CD30-L/CD30 in Inflammatory Bowel Disease2006

    • Author(s)
      Shinichi, Somada, Hiromi, Muta, Kazuhiko, Nakamura, Kuniomi, Honda, Naomi, Higuchi, Takahiro, Mizutani, Kenji, Kanayama, Yorinobu, Sumida, Shigetaka, Yoshinaga, Souichi, Itaba, Hirotada, Akiho, Ryoichi, Takayanagi Kenzaburo, Tani
    • Organizer
      DDW(Japan) 2006
    • Place of Presentation
      Sapporo Japan
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary

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Published: 2006-04-01   Modified: 2016-04-21  

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