| Project/Area Number |
20591191
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Saitama Medical University |
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Principal Investigator |
NAGATA Makoto Saitama Medical University, 医学部, 教授 (20211443)
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| Project Period (FY) |
2008 – 2010
|
| Project Status |
Completed (Fiscal Year 2010)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | アレルギー / 重症喘息 / 好球 / 好酸球 / Th1 / TXB2 / IP-10 / 好中球性炎症Interleukin-8 / Tumor necrosis factor-α / Interleukin-13 / β2受容体刺激薬 / 吸入ステロイド薬 / 好中球 / Interleukin-8 / Interferon-γ / Interferon-β |
|---|
| Research Abstract |
In the pathogenesis of severe asthma, not only eosinophils but also neutrophils play important roles. We previously reported a positive correlation between the concentrations of neutrophils and eosinophils in induced sputum from patients with severe, corticosteroid-dependent asthma. Furthermore, we reported that, even in the absence of chemoattractant for eosinophils, neutrophils stimulated by IL-8 are capable of inducing the trans-basement membrane migration of eosinophils, suggesting that IL-8-stimulated neutrophils lead eosinophils to accumulate in the airways of asthmatic patients. In this study, we further elucidated the pathogenesis of airway inflammation in refractory asthma. We found that concentrations of IL-8 in induced sputa are higher in severe asthmatics than in mild asthmatics. Further, concentrations of TXB2 or LTB4 in EBC also increased in unstable or severe asthma. IFNs augment eosinophil adhesion-inducing activity of endotherial cells. Salbutamol increases IL-13 and decreases IFN-γ production by mononuclear cells from allergic asthmatics. Finally, CXCR3 ligands including IP-10 increase adhesiveness and superoxide anion production of eosinophils. These findings are thought to play important roles in the pathogenesis of severe asthma.
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