| Project/Area Number |
17K09628
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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 |
Respiratory organ internal medicine
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| Research Institution | Kyorin University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
皿谷 健 杏林大学, 医学部, 准教授 (40549185)
滝澤 始 杏林大学, 医学部, 教授 (80171578)
田村 仁樹 杏林大学, 医学部, 助教 (80616607)
本多 紘二郎 杏林大学, 医学部, 助教 (20802995)
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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 |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 喘息 / 好中球 / IL-33 / sST2 / ST2 / 重症喘息 / 気管支上皮細胞 / 感染 / 免疫 / バイオマーカー |
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| Outline of Final Research Achievements |
Neutrophilic asthma, characterized by neutrophil accumulation in the airways, is the most severe phenotype of asthma; thus, a strategy for controlling airway neutrophilia is desired to treat patients with severe asthma. We previously reported that sST2, a decoy receptor for IL-33, is associated with neutrophilic airway disease. Here, we hypothesized that sST2 plays a crucial role in pathogenesis of neutrophilic asthma. To address this, we conducted a clinical study assessing sputum and breath condensate from asthmatics and in vitro experiments using bronchial epithelial cells. We discovered that IL-33 facilitates airway neutrophilia, and that sST2 is an intrinsic regulator that ameliorates IL-33-related airway inflammation.
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| Academic Significance and Societal Importance of the Research Achievements |
我々は、喘息患者の喀痰や呼気の解析と気管支上皮細胞の培養実験を組み合わせたトランスレーショナルリサーチを行った。その結果、喫煙、酸化ストレス、および好中球エラスターゼが気管支上皮細胞でIL-33の発現と放出を促進することと、IL-33は気管支上皮細胞のサイトカイン産生を増強して好中球性炎症を惹起することを発見した。sST2は重症喘息のバイオマーカーであるが、生理的な意義は抗炎症作用であった。我々の成果は、sST2補充療法が重症喘息の新規治療戦略になり得ることを示している。
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