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Therapy for collagen diseases by using chemokine antagonists

Research Project

Project/Area Number 14570414
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionEhime University

Principal Investigator

HASEGAWA Hitoshi  Ehime University Hospital, Lecturer, 医学部附属病院, 講師 (40164826)

Co-Investigator(Kenkyū-buntansha) NOSE Masato  Ehime University, School of Medicine, Professor, 医学部, 教授 (70030913)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
KeywordsChemokines / Chemokine antagonists / Collagen diseases / MRL / lpr mouse / lpr mouse
Research Abstract

The use of receptor antagonists for chemokines is an alternative approach to blocking cnemokine actions and has the potential to provide novel therapeutics for autoimmune diseases. The NH_2-terminally truncated MCP-1 or fractalkine analogues were converted to secreting forms, inserted into the pCXN2 expression vector and transfected into a non-metastatic fibroblastoid cell tin. MRL/N-1. MCP-1-antagonist-or fractalkine-antagonist-transfected MRL/N-1 cells were injected subcutaneously into MRL/lpr mice aged 7 wk (before the initiation of lupus nephritis) and 12 wk (at the early stage of the disease) After 8 weeks, MCP-1-antagonist-and fractalkine-antagonist-bearing mice showed markedly diminished infiltration of macrophages and T cells, glomerular hypercellularity, glomerulosclerosis, crescent formation and also vasculitis compared with control mice. In addition, MCP-1-antagonist-bearing mice ameliorated the progression of sialadenitis compared with control mice. To determine whether SLC antagonist inhibits the development of chronic GVHD, chronic GVHD was induced by injecting DBA/2 spleen cells into (C57BL/6 X DBA/2) F1 mice. Total numbers of spleen cells and host B cells, serum levels of IgE, and of total IgG and IgG1 of anti-DNA antibodies in SLC antagonist-treated GVHD mice were significantly lower than those in control PBS-treated GVHD mice. This result suggests that SLC antagonist has beneficial effects for the prevention of chronic GVIHD.

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (19 results)

All Other

All Publications (19 results)

  • [Publications] Hasegawa, H. et al.: "Antagonist of monocyte chemoattractant protein 1 (CCL2) prevents the initiation and progression of lupus nephritis and renal vasculitis in MRL/1pr mice"Arthritis and Rheumatism. 48. 2555-2566 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sasaki, M., Hasegawa, H.et al.: "Antagonist of secondary lymphoid-tissue chemokine (CCL21) prevents the development of chronic graft-versus-host disease in mice"Journal of Immunology. 170. 588-596 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakatani, K., Fujii, H., Hasegawa, H.et al.: "Endothelial adhesion molecules in glomerular lesions : Association with their severity and diversity in lupus models."Kidney International. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] 長谷川 均: "自己免疫疾患における分子標的遺伝子治療の展望-ケモカインアンタゴニスト"臨床免疫. 40. 668-675 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kohno, M., Hasegawa, H.: "Chemokines and autoimmune diseases"Recent Research Developments in Immunology. 4. 115-126 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hasegawa, H. et al.: "CCR7 chemokine receptor expression on normal lymphocyte subsets and adult T-cell leukemia cells."Leucocyte Typing. VII. 255-258 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hasegawa H., Kohono, M., Sasaki, M., Inoue, A., Ito, MR, Terada, M., Hieshima, K., Maruyama, H., Miyazaki, J., Yoshie, O., Nose, M., Fujita, S.: "Antagonist of monocyte chemoattractant protein 1 ameliorates the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice."Arthritis & Rheumatism. 48. 2555-2566 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Sasaki, M., Hasegawa, H., Kohno, M, Inoue, A., Ito, MR, Fujita, S.: "Antagonist of secondary lymphoid-tissue chemokine (CCR ligand 21) prevents the development of chronic graft-versus-host disease in mice."Journal of Immunology. 170. 588-596 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Nakatani, K., Fujii, H., Hasegawa, H., Terada, M., Arita, N., Ito, MR., Ono, M., Yoshimoto, S., Iwano, M., Nose, M.: "Endothelial adhesion molecules in glomerular lesions : Association with their severity and diversity in lupus models."Kidney International. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Haseeawa, H.: "Chemokine antagonist."Rinshomeneki. 40. 668-675 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Kohno, M., Hasegawa, H.: "Chemokines and autoimmune diseases"Recent Research Developments in Immunology. 4. 115-126 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hasegawa, H., Kohno, M., Nomura, T., Sasaki, M., Yoshie, O., Fujita, S.: "CCR7 chemokine receptor expression on normal lymphocyte subsets and adult T-cell leukemia cells."Leucocyte Typing VII (Mason, DY et al. Eds.)(Oxford University Press). 255-258 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Hasegawa, H. et al.: "Antagonist of monocyte chemoattractant protein 1 (CCL2) prevents the initiation and progression of lupus nephritis and renal vasculitis in MRL/1pr mice"Arthritis and Rheumatism. 48. 2555-2566 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Sasaki, M., Hasegawa, H.et al.: "Antagonist of secondary lymphoid-tissue chemokine (CCL21) prevents the development of chronic graft-versus-host disease in mice"Journal of Immunology. 170. 588-596 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Nakatani, K., Fujii, H., Hasegawa, H.et al.: "Endothelial adhesion molecules in glomerular lesions : Association with their severity and diversity in lupus models."Kidney International. (in press).

    • Related Report
      2003 Annual Research Report
  • [Publications] 長谷川 均: "自己免疫疾患における分子標的遺伝子治療の展望ケモカインアンタゴニスト"臨床免疫. 40. 668-675 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hasegawa, H., et al.: "Antagonist of monocyte chemoattractant protein 1 (CCL2) prevents the initiation and progression of lupus nephritis and renal vasculitis in MRL/lpr mice"Arthritis and Rheumatism. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] Sasaki, M., Hasegawa, H., et al.: "Antagonist of secondary lymphoid-tissue chemokine (CCL21) prevents the development of chronic graft-versus-host disease in mice"Journal of Immunology. 170. 588-596 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kohno, M., Hasegawa, H.: "Chemokines and autoimmune diseases"Recent Research Developments in Immunology. 4. 115-126 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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