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A Study of Activation and Apoptosis of Peripheral Blood Mononuclear Cells and Lamina Propria Mononuclear Cells in Inflammatory Bowel Diseases

Research Project

Project/Area Number 16590586
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

ANDO Takafumi (2005)  Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (80378041)

楠神 和男 (2004)  名古屋大学, 医学部附属病院, 助教授 (00234427)

Co-Investigator(Kenkyū-buntansha) NIWA Yasumasa  Nagoya University, University Hospital, Assistant Professor, 医学部附属病院, 講師 (20283442)
OHMIYA Naoki  Nagoya University, University Hospital, Research Associate, 医学部附属病院, 助手 (00335035)
安藤 貴文  名古屋大学, 医学部付属病院, 助手 (80378041)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsInflammatory bowel diseases / lamina propria mononuclear cells / CD4-positive T cells / apoptosis / anti-cytokine therapy / anti-TNF-alpha antibody / prediction of treatment efficacy / 潰瘍性大腸炎 / クローン病 / T細胞 / 活性化
Research Abstract

Peripheral blood mononuclear cells (PBMCs) and lamina propria mononuclear cells (LPMCs) were isolated from the peripheral venous blood and the surgical specimens, respectively, by 6% dextran sedimentation followed by density gradient centrifugation on Ficoll-Hypaque. From PBMCs and LPMCs, CD4-positive T cells were isolated using magnetic cell sorting. Flow cytometric analysis confirmed that isolated CD4-positive T cells were very pure (PBMCs: 99.0±0.3%, LPMCs: 98.5±0.4%). CD4-positive T cells were cultured in microwell plates coated with anti-CD3 and anti-CD28 antibodies. The expression of IL-2 receptor (IL-2R) alpha chain and membranous type TNF-alpha mRNA were peaked after 96h in CD4-positive T cells from either PBMCs or LPMCs. Both IL-2R and TNF-alpha mRNA expressions were detected more commonly in CD4-positive T cells from LPMCs compared with CD4-positive T cells from PBMCs. A chimeric anti-TNF-alpha antibody (infliximab) has induced apoptosis on CD4-positive T cells, which indicat … More es that it might be possible to predict the efficacy of drugs before treatment in vitro. Thirteen patients with Crohn's Disease were treated with infliximab. Clinical response was evaluated using the Crohn's Disease Activity Index (CDAI), and serum soluble IL-2 receptor (sIL-2 R), IL-6, and TNF-alpha levels were analyzed by ELISA before and after treatment. Apoptosis of peripheral and lamina propria T-lymphocytes after culture with infliximab was detected by flow cytometry. CDAI and serum sIL-2 R, IL-6 and TNF-alpha levels decreased in most patients after treatment with infliximab. Serum TNF-alpha levels before treatment in the six patients in whom CDAI decreased by more than 70 were less than 5 ng/ml. Infliximab induced the apoptosis of lamina propria but not peripheral T-lymphocytes. A low level of serum TNF-alpha might be an indicator for infliximab treatment. The induction of apoptosis of lamina propria T-lymphocytes by anti-cytokine drugs may be one of the important mechanisms of their anti-inflammatory effect in patients with inflammatory bowel disease. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (12 results)

All 2006 2005 2004

All Journal Article (12 results)

  • [Journal Article] Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis2006

    • Author(s)
      Ryuichi Furuta, Takafumi Ando, Hidemi Goto, etal.
    • Journal Title

      Journal of Gastroenterology and Hepatology (inpress)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Rebamipide enema therapy as a treatment for patients with active distal ulcerative colitis2006

    • Author(s)
      Ryuichi Furuta, Takafumi Ando, Hidemi Goto, et al.
    • Journal Title

      Journal of Gastroenterology and Hepatology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Possible involvement of the interleukin-15 and interleukin-15 receptor system in a heightened state of lamina propria B cell activation and differentiation in patients with inflammatory bowel disease2005

    • Author(s)
      Tsuyoshi Nishiwaki, Hidemi Goto, Takafumi_Ando, _etal.
    • Journal Title

      Journal of Gastroenterology 40

      Pages: 128-36

    • NAID

      10014513492

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 炎症性腸疾患における炎症性/抗炎症性サイトカイン・インバランス2005

    • Author(s)
      楠神和男, 伊奈研次, 安藤貴文, 後藤秀実
    • Journal Title

      G.I.Research 13

      Pages: 3-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 難治性潰瘍性大腸炎に対する新しい治療 免疫抑制剤を中心に2005

    • Author(s)
      安藤貴文, 高橋宏尚, 渡辺 修, 後藤秀実
    • Journal Title

      胃と腸 40

      Pages: 1383-1388

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Possible involvement of the interleukin-15 and interleukin-15 receptor system in a heightened state of lamina propria B cell activation and differentiation in patients with inflammatory bowel disease2005

    • Author(s)
      Tsuyoshi Nishiwaki, Hidemi Goto, Takafumi Ando, et al.
    • Journal Title

      Journal of Gastroenterology 40

      Pages: 128-136

    • NAID

      10014513492

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Unbalance of inflammatory and anti-inflammatory cytokines in inflammatory bowel diseases2005

    • Author(s)
      Kazuo Kusugami, Kenji Ina, Takafumi Ando, Hidemi Goto
    • Journal Title

      G.I.Research 13

      Pages: 3-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] New therapies for Refractory Ulcerative Colitis -focused on immunosuppressive agents-2005

    • Author(s)
      Takafumi Ando, Hironao Takahashi, Osamu Watanebe, Hidemi Goto
    • Journal Title

      I to Cho 40

      Pages: 1383-1388

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Possible involvement of the interleukin-15 and interleukin-15 receptor system in a heightened state of lamina propria B-cell activation and differentiation in patients with inflammatory bowel disease.2005

    • Author(s)
      Tsuyoshi Nishiwaki
    • Journal Title

      Journal of Gastroenterology 40・2(in press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Immunomodulatory therapy for inflammatory bowel disease2004

    • Author(s)
      Kazuc Kusugami, Kenji Ina, Takafurni_Ando, Kenji Hibi, Yuji_Nishio, Hidemi_Goto
    • Journal Title

      Journal of Gastroenterology 39

      Pages: 1129-1137

    • NAID

      10014091493

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunomodulatory therapy for inflammatory bowel disease2004

    • Author(s)
      Kazuo Kusugami, Kenji Ina, Takafumi Ando, Kenji Hibi, Yuji Nishio, Hidemi Goto
    • Journal Title

      Journal of Gastroenterology 39

      Pages: 1129-1137

    • NAID

      10014091493

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunomodulatory therapy for inflammatory bowel disease.2004

    • Author(s)
      Kazuo Kusugami
    • Journal Title

      Journal of Gastroenterology 39・12

      Pages: 1129-1137

    • NAID

      10014091493

    • Related Report
      2004 Annual Research Report

URL: 

Published: 2004-04-01   Modified: 2016-04-21  

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