Establishment of prevention and treatment strategy of asthma exacerbation
| Project/Area Number |
15K09228
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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 |
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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: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 喘息増悪 / 気管支喘息 / 増悪 / ウィルス感染 / 好酸球 / ライノウィルス / 好中球 |
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| Outline of Final Research Achievements |
Eosinophils are involved in the development of asthma exacerbation. Interleukin (IL)-5 is most important cytokine to induce eosinophilic inflammation. However, other mechanism than IL-5 may play roles in the induction or maintenance of eosinophilic airway inflammation.
In the case of severe asthma, both eosinophils and neutrophils contribute to its pathogenesis. In this study, we found that neutrophils from severe asthmatics can induce the transbasement membrane migration of eosinophils. Periostin is an extracellular matrix protein regulated by Th2 cytokines, such as IL-13, and is a biomarker of Th2-mediated immune responses in bronchial asthma. In this study, we found that periostin activates eosinophil functions. A major cause of asthma exacerbation is viral infection, especially rhinovirus (RV) infection. Cadherin-related family member (CDHR) 3 is a receptor for RV-C, which is closely linked to wheezing illnesses. In this study, we found that CDHR3 activates eosinophil functions.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、好酸球活性化には様々な機序が関与することが確認された。我々は以前より、IL-5非依存性の好酸球活性化機序として、①GM-CSFなどの他の2型サイトカイン②システイニルロイコトリエン③ウィルス感染時に発現亢進するCXCR3 ligandsなどが直接好酸球を活性化し、喘息増悪の誘導に関与しうることを明らかにしてきた。今回の研究でさらに①活性化好中球②細胞外マトリックス蛋白ペリオスチン③RV-Cの受容体であるCDHR3が好酸球を直接活性化し、喘息増悪における気道炎症の成立に関与しうることを明らかにした。これら好酸球活性化機序の解明は、喘息増悪の予防および治療戦略の立脚に重要と考えられた。
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Report
(5 results)
Research Products
(36 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
Issue: 3
Pages: 264-271
DOI
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Peer Reviewed
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[Presentation] Elevated periostin concentrations in the bronchoalveolar lavage fluid of eosinophilic pneumonia.2018
Author(s)
Kazuyuki Nakagome, Yutaka Nakamura, Takehito Kobayashi, Shoichiro Ohta, Junya Ono, Kiyoko Kobayashi, Kenji Ikebuchi, Toru Noguchi, Tomoyuki Soma, Kohei Yamauchi, Kenji Izuhara, Makoto Nagata.
Organizer
ATS Conference 2018
Related Report
Int'l Joint Research
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[Presentation] 好酸球性肺炎の気管支肺胞洗浄液におけるペリオスチン及びサイトカイン濃度の解析.2017
Author(s)
中込 一之, 中村 豊, 小林 威仁, 太田 昭一郎, 小野 純也, 野口 哲, 杣 知行, 坂本 芳雄, 山内 広平, 出原 賢治, 永田 真
Organizer
第66回日本アレルギー学会学術大会ミニシンポジウム
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