| Project/Area Number |
26462581
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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 |
Otorhinolaryngology
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
神前 英明 滋賀医科大学, 医学部, 講師 (10402710)
清水 志乃 滋賀医科大学, 医学部, 医員 (50505592)
戸嶋 一郎 滋賀医科大学, 医学部, 助教 (80567347)
小河 孝夫 滋賀医科大学, 医学部, 講師 (90549908)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
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| Keywords | 好酸球性副鼻腔炎 / ＥＧＦ受容体阻害薬 / 組織リモデリング / 鼻茸形成 / ラット鼻粘膜 / 鼻粘膜上皮細胞 / 線維芽細胞 / サイトカイン / ＥＧF受容体阻害薬 / 好酸球 / 上皮細胞 / ＭＵＣ５ＡＣ / ＩＬ－８ / ＥＧＦ受容体 / ＬＰＳ / 杯細胞化生 / ＴＮＦ－alpha / amphiregulin / TGF-alpha / IL-8 |
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| Outline of Final Research Achievements |
We examined the mechanism of tissue remodeling in the pathogenesis of eosinophilic chronic rhonosinusitis. Coagulation factors such as thrombin and FXa stimulate the secretion of profibrotic cytokines and MUC5AC mucin from nasal epithelial cells or fibroblasts. Eosinophil-epithelial cell and eosinophil-fibroblast interactions also stimulate the secretion of cytokines and MUC5AC mucin. EGF receptor inhibitor AG1478 significantly inhibited these secretion of cytiokines and MUC5AC mucin induced by thrombin and by eosinophil-epithelial cell or eosinophil-fibroblast interactions, and EGFR transactivation plays a crucial role. Intraperitoneal injection or intranasal instillation of EGFR inhibitor AG1478 significantly inhibited LPS-induced or antigen-induced goblet cell metaplasia, mucus production and eosinophil/neutrophil infiltration in rat nasal epithelium. Intranasal instillation of EGFR inhibitor may be a new therapeutic approach for the treatment of eosinophilic chronic rhinosinusitis.
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