Research in Mechanisms of Action Regarding Inhibitory Effects of Interferon-γ and -β in Intracellular Signal Transduction.
| Project/Area Number |
14570569
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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 |
Respiratory organ internal medicine
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| Research Institution | Nippon Medical School |
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Principal Investigator |
AZUMA Arata Nippon Medical School, Respiratory Medicine, Assistant Professor, 医学部, 講師 (10184194)
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| Co-Investigator(Kenkyū-buntansha) |
KUDOH Shoji Nippon Medical School, Respiratory Medicine, Professor, 大学院・医学研究科, 教授 (40256912)
HASHIMOTO Shu Nihon University, 1^<st> Department of Internal Medicine, 医学部, 講師 (30159090)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2003: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Interferon-g / Interferon-b / Pulmonary Fibrosis / Interstitial Pneuminia / Fibroblast |
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| Research Abstract |
Purpose :
Though idiopathic pulmonary fibrosis(IPF) is fatal disease in field of diffuse lung diseases, no effective treatment improving prognosis has been reported. Interferons will be promising for treatment in fibrotic disorders in pulmonary disease, however, Interferon-β has been failed to improve survival ratio of IPF and interferon-γ fairly improved %VC in early stage of IPF (%VC>60%). Based on these clinical situations, we investigated mechanism of action of interferon-□ in bleomycin induced pulmonary fibrosis.
Methods :
Bleomycin at day 0 and interferon-β for 4 weeks were administered intravenously to ICR mice. At 28 days after bleomycin injection, histological and chemical analysis was performed for evaluation of effects of interferon-β. Tissue distribution and amounts of TGF-β1 and thrombospondin-1/2 were analyzed.
Results and Discussion :
Interferon-β□ attenuated prolylhydroxylase activity, resulting in inhibition of pulmonary fibrosis. Bleomycin-induced increase in TGF-β1 in epithelial cells and extracellular matrix was attenuated by interferon-β. Thrombospondin-1/2 was limited in platelets of control mice, but was present in foamy cells in fibrotic regions induced by bleomycin. In vitro study, IFN-g (10-1000ug/ml) did not inhibit growth of HMg2980 lung fibroblast cell line under no stimulation, but inhibited TGF-β1-induced proliferation of HMg2980 cell line.
These findings suggest that the antifibrotic effect of interferon-β□ is inhibition of TGF-βand its activation via decrease in thrombospondin-1/2 in lung tissue and change in location of thrombospondin-1/2 from platelets to foamy cells. IFN-β and IFN-γ will be promising agents in different mechanisms to inhibit fibroblast proliferation.
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] Interferon-□ Inhibits Bleomycin-Induced Lung Fibrosis by Decreasing TGF-β and Thrombospondin.2005
Author(s)
A Azuma, YJ Li, J Usuki, S Abe, K Matsuda, S Henmi, Y Miyauchi, A Izawa, S Sone, S Hashimoto, S Kudoh
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Journal Title
Am J Respir Crit Care Med 171
Pages: 1040-1047
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Vegetable, Fruit, and Cereal Intake and Risk of Idiopathic Pulmonary Fibrosis in Japan.2005
Author(s)
Y Miyake, S Sasaki, T Yokoyama, K Chida, A Azuma, T Suda, S Kudoh, N Sakamoto, K Okamoto, G Kobashi, M Washio, Y Inaba, H Tanaka
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Journal Title
Experimental Lung Research (in press)
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] A Double Blind And Placebo-Controlled Clinical Study Of Pirfenidone In Patients With Idiopathic Pulmonary Fibrosis.2004
Author(s)
A Azuma, T Nukiwa, E Tsuboi, M Suga, S Abe, K Nakata, Y Taguchi, S Nagai, H Itoh, M Ohi, A Sato, S Kudoh, Members of Research Group for Diffuse Lung Diseases in Japan, G Raghu
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Journal Title
Annals of Neutrition and Metabolism 48(6)
Pages: 390-397
Description
「研究成果報告書概要(欧文)」より
Related Report
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