The establishment of novel treatment for systemic lupus erythematosus using JAK inhibitor
Project/Area Number |
15K08107
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Medical pharmacy
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Research Institution | Juntendo University |
Principal Investigator |
IKEDA Keigo 順天堂大学, 医学部, 准教授 (40465068)
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Co-Investigator(Kenkyū-buntansha) |
関川 巖 順天堂大学, 医学部, 助教授 (80179332)
佐藤 実 産業医科大学, 産業保健学部, 教授 (90162487)
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Co-Investigator(Renkei-kenkyūsha) |
TAKASAKI Yoshinari 順天堂大学, 医学部, 教授 (80154772)
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Research Collaborator |
HAYAKAWA Kunihiro 順天堂大学, 大学院環境医学研究所
FUJISHIRO Maki 順天堂大学, 大学院環境医学研究所
KAWASAKI Mikiko 順天堂大学, 大学院環境医学研究所
SUZUKI Satoshi 順天堂大学, 大学院環境医学研究所
MIYASHITA Tomoko 順天堂大学, 大学院環境医学研究所
HIRAI Takuya 順天堂大学, 大学院環境医学研究所
TSUSHIMA Hiroshi 順天堂大学, 大学院環境医学研究所
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Project Period (FY) |
2015-04-01 – 2018-03-31
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Project Status |
Completed (Fiscal Year 2017)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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Keywords | 全身性エリテマトーデス / JAK阻害薬 / I型インターフェロン / IFIT3 / T細胞 / Ⅰ型インターフェロン / ISG15 / インターフェロン |
Outline of Final Research Achievements |
We evaluated the efficacy of the JAK inhibitor tofacitinib (TOFA) for controlling IFN signalling via the JAK-STAT pathway and as a therapeutic for SLE in this research project. We treated NZB/NZW F1 mice with TOFA and assessed alterations in their disease, pathological, and immunological conditions. Gene-expression results obtained from CD4+ T cells (SLE mice) and CD3+ T cells (human SLE patients) were measured by DNA microarray and qRT-PCR. TOFA treatment resulted in reduced levels of anti-dsDNA antibodies, decreased proteinuria, and amelioration of nephritis as compared with those observed in control animals. We also detected decreased expression of several IFN-signature genes Ifit3 and Isg15 in CD4+ from SLE-prone mice following TOFA and DEXA treatment, and IFIT3 in CD3+ T cells from human patients following immunosuppressant therapy including steroid, respectively. Our results suggest that TOFA could be utilised for the development of new SLE-specific therapeutic strategies.
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Report
(4 results)
Research Products
(11 results)
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[Journal Article] The effectiveness of new triple combination therapy using synthetic disease-modifying anti-rheumatic drugs with different pharmacological function against rheumatoid arthritis: the verification by an in vitro and clinical study.2017
Author(s)
Hirai T, Ikeda K, Fujishiro M, Tsushima H, Hayakawa K, Suzuki S, Yamaguchi A, Nozawa K, Morimoto S, Takasaki Y, Ogawa H, Takamori K, Tamura N, Sekigawa I
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Journal Title
Clin Rheumatol
Volume: 36
Issue: 1
Pages: 51-58
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] A re-evaluation of anti-NA-14 antibodies in patients with primary Sjogren's syndrome: Significant role of interferon-γ in the production of autoantibodies against NA-14.2016
Author(s)
Uomori K, Nozawa K, Ikeda K, Doe K, Yamada Y, Yamaguchi A, Fujishiro M, Kawasaki M, Morimoto S, Takamori K, Sekigawa I, Chan EK, Takasaki Y.
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Journal Title
Autoimmunity.
Volume: 49
Issue: 5
Pages: 347-56
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Inhibition of each module of connective tissue growth factor as a potential therapeutic target for rheumatoid arthritis.2015
Author(s)
Miyashita T, Morimoto S, Fujishiro M, Hayakawa K, Suzuki S, Ikeda K, Miyazawa K, Morioka M, Takamori K, Ogawa H, Sekigawa I, Takasaki Y.
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Journal Title
Autoimmunity
Volume: 49(2)
Issue: 2
Pages: 109-14
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Inhibition of the insulin-like growth factor system is a potential therapy for rheumatoid arthritis.2014
Author(s)
Suzuki S, Morimoto S, Fujishiro M, Kawasaki M, Hayakawa K, Miyashita T, Ikeda K, Miyazawa K, Yanagida M, Takamori K, Ogawa H, Sekigawa I, Takasaki Y
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Journal Title
Autoimmunity
Volume: -
Issue: 4
Pages: 251-8
DOI
Related Report
Peer Reviewed / Open Access
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