2003 Fiscal Year Final Research Report Summary
Therapy for collagen diseases by using chemokine antagonists
| Project/Area Number |
14570414
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
内科学一般
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| Research Institution | Ehime University |
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Principal Investigator |
HASEGAWA Hitoshi Ehime University Hospital, Lecturer, 医学部附属病院, 講師 (40164826)
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| Co-Investigator(Kenkyū-buntansha) |
NOSE Masato Ehime University, School of Medicine, Professor, 医学部, 教授 (70030913)
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| Project Period (FY) |
2002 – 2003
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| Keywords | Chemokines / Chemokine antagonists / Collagen diseases / MRL / lpr mouse |
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| 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.
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[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)
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「研究成果報告書概要(欧文)」より
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[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)
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「研究成果報告書概要(欧文)」より
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[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).
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[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)
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「研究成果報告書概要(欧文)」より
