Development of refined detection system for mature and active IL-1b family proteins
| Project/Area Number |
17K08983
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | Shimane University |
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Principal Investigator |
Takeshi Urano 島根大学, 学術研究院医学・看護学系, 教授 (70293701)
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| Co-Investigator(Kenkyū-buntansha) |
杉浦 智子 島根大学, 医学部, 特別協力研究員 (60647402)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 炎症 / IL-1β / IL-18 / 測定キット / モノクローナル抗体 / バイオ医薬品 / 炎症性サイトカイン / 臨床検査医学 |
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| Outline of Final Research Achievements |
Inflammation is a common risk factor for common diseases, such as cancer, and autoimmune disease. Interleukin‐1b and IL-18 are pro-inflammatory cytokines assigned to the IL-1 family because of its structural homology, receptor utilization and signal transduction pathways. Both of IL-1b and IL-18 are initially synthesized as inactive precursors and the cleavage required for processing into mature forms is mainly mediated by pro-inflammatory caspases following the activation and assembly of macromolecular complexes called inflammasomes. Detection of these neoepitopes of mature forms should provide a unique and sensitive indicator of inflammatory action.
A refined detection system for mature and active IL-1b and IL-18 could be developed by utilizing our developed neoepitope mAbs in combination with epitope-different mAbs. Such a system might be useful in inflammasome biology, and for diagnostic and therapeutic strategies for inflammatory diseases.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により開発したモノクローナル抗体により、炎症状態を正確に把握した臨床症状を反映した簡便・迅速・正確な測定法を確立することができる。その測定法を利用することで、迅速な診断および正確な治療法の選択が可能となる。さらに、開発したモノクローナル抗体をヒト化することで治療用のバイオ医薬品として開発を進めている。
特に、IL-18に対するモノクローナル抗体はウエスタンブロット・免疫沈降・細胞免疫染色に利用できるばかりでなく、IL-18 の機能を阻害した。既存の抗体では成し得なかった、患者血液を用いたウエスタンブロット解析で活性型 IL-18を提示できるほど検出感度が優れていた。
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] Uric acid-mediated inflammasome activation in IL-6 primed innate immune cells is regulated by baricitinib.2020
Author(s)
Temmoku J, Fujita Y, Matsuoka N, Urano T, Furuya MY, Asano T, Sato S, Matsumoto H, Watanabe H, Kozuru H, Yatsuhashi H, Kawakami A, Migita K.
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Journal Title
Mod Rheumatol.
Volume: 30
Issue: 1
Pages: 1-6
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Hydroxychloroquine inhibits IL-1β production from amyloid-stimulated human neutrophils.2019
Author(s)
Fujita Y, Matsuoka N, Temmoku J, Furuya MY, Asano T, Sato S, Kobayashi H, Watanabe H, Suzuki E, Urano T, Kozuru H, Yatsuhashi H, Koga T, Kawakami A, Migita K.
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Journal Title
Arthritis Res Ther.
Volume: 21(1)
Issue: 1
Pages: 250-250
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Generation and characterization of antagonistic anti-human interleukin (IL)-18 monoclonal antibodies with high affinity: Two types of monoclonal antibodies against full-length IL-18 and the neoepitope of inflammatory caspase-cleaved active IL-18.2019
Author(s)
Nariai Y, Kamino H, Obayashi E, Kato H, Sakashita G, Sugiura T, Migita K, Koga T, Kawakami A, Sakamoto K, Kadomatsu K, Nakakido M, Tsumoto K, Urano T.
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Journal Title
Archives of Biochemistry and Biophysics
Volume: 663
Pages: 71-82
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate.2018
Author(s)
Ganasen M, Togashi H, Takeda H, Asakura H, Tosha T, Yamashita K, Hirata K, Nariai Y, Urano T, Yuan X, Hamza I, Mauk AG, Shiro Y, Sugimoto H, Sawai H.
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Journal Title
Communications Biology
Volume: 1
Issue: 1
Pages: 120-120
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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