| Project/Area Number |
18K16886
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Tsuda Takeshi 大阪大学, 医学部附属病院, 医員 (00778631)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2019: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000)
Fiscal Year 2018: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
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| Keywords | Semaphorin / ECRS / SEMA4D / 好酸球性副鼻腔炎 / 中和抗体 |
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| Outline of Final Research Achievements |
Serum soluble SEMA4D levels were elevated in patients with ECRS and positively correlated with disease severity. SEMA4D treatment increased the permeability of endothelial cells through the activation of RhoA, permitting eosinophils to migrate easily across the endothelium. Recombinant SEMA4D proteins activated RhoA and significantly increased the permeability of HNEpCs, as did vascular endothelium. Paranasal inflammation was less severe in SEMA4D-/- mice than in WT mice. Treatment with anti-SEMA4D antibody ameliorated eosinophilic infiltration in sinus tissues and nasal lavage fluid in the ECRS animal model.
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| Academic Significance and Societal Importance of the Research Achievements |
難治性疾患である好酸球性副鼻腔炎において、SEMA4Dが血管内皮および鼻腔上皮の透過性亢進および炎症性サイトカイン産生という作用を開始して病態を増悪させるという新たなメカニズムを発見した。またマウスモデルにおいてSEMA4D中和抗体投与によって好酸球性炎症が軽快する所見を得られたことからSEMA4Dが好酸球性副鼻腔炎における新たな治療ターゲットとなる可能性が見いだされた。
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