The study of purinergic signaling in neutrophil-related allergic airway inflammation of asthma
| Project/Area Number |
15K09188
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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 | Saitama Medical University |
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Principal Investigator |
Soma Tomoyuki 埼玉医科大学, 医学部, 准教授 (40307921)
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| Co-Investigator(Kenkyū-buntansha) |
中込 一之 埼玉医科大学, 医学部, 准教授 (60401113)
小林 威仁 埼玉医科大学, 医学部, 准教授 (90618266)
原 健一郎 群馬大学, 大学院医学系研究科, 助教 (70436301)
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| Research Collaborator |
UCHIDA yoshitaka
YOKOTA akemi
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| Project Period (FY) |
2015-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | ATP / 重症喘息 / 好中球 / 好中球エラスターゼ / 好酸球組織間隙遊走能 / P2Y2受容体 / 呼吸機能 / エンドトキシン / 喀痰好中球比率 / P2Y2レセプター / 好酸球遊走能 / P2レセプター / 喘息 / 喀痰 / 好酸球 / 細胞間隙遊走能 |
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| Outline of Final Research Achievements |
Danger signals are known as players that have an ability to spread signal of inflammation in tissue. Those mediators are released from injured or dead cells. We, comprehensively, determined whether an adenosine triphosphate (ATP) contributes to pathophysiology in asthma. 1) Concentrations of ATP in sputum were increased in patients with severe asthma than those with non-severe asthma. Increases in sputum ATP concentration were correlated with increases in sputum neutrophil ratio, concentration of sputum neutrophilic elastase and deterioration of pulmonary function in patients with asthma, especially, severe asthma. 2) ATP were involved in trans-basement membrane
migration of eosinophils induced by LPS-stimulated neutrophils from human
peripheral blood through P2Y2 receptors. 3) Airway exposure of LPS and Staphylococcus aureus particles-sensitized mice to OVA induces Th2 and Th17-type immune responses. Further study is needed to determine involvement of ATP in this response.
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| Academic Significance and Societal Importance of the Research Achievements |
気管支喘息はTh2型免疫応答と2型自然免疫リンパ球が機能するType2炎症を主体とする慢性アレルギー性気道炎症疾患である。疾患の多様性が明らかになるに従い、その機序も一元的な説明が困難となっている。本研究ではATPというdanger signalが喘息の病態形成に関与することを示唆した新しい知見といえる。臨床的な関連性を示すとともに、既存の免疫応答とは異なる経路で炎症が進展することを細胞実験で見出している点で、意義があると推察する。また本研究の結果は好中球性喘息の病態解明の一助となると考えられる。将来的に、ATPを介した免疫応答を適正に抑制する機序が見出されると、治療につながると期待される。
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Report
(5 results)
Research Products
(49 results)
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[Journal Article] Elevated Periostin Concentrations in the Bronchoalveolar Lavage Fluid of Patients with Eosinophilic Pneumonia.2019
Author(s)
Nakagome K, Nakamura Y, Kobayashi T, Ohta S, Ono J, Kobayashi K, Ikebuchi K, Noguchi T, Soma T, Yamauchi K, Izuhara K, Nagata M.
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Journal Title
Int Arch Allergy Immunol.
Volume: 178(3)
Pages: 264-271
Related Report
Peer Reviewed
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