2022 Fiscal Year Final Research Report
Functional analysis and therapeutic strategy of TRPV3 in eosinophilic chronic rhinosinusitis
Project/Area Number |
20K09753
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Review Section |
Basic Section 56050:Otorhinolaryngology-related
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Research Institution | University of Fukui |
Principal Investigator |
Kato Yukinori 福井大学, 学術研究院医学系部門(附属病院部), 助教 (00748981)
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Project Period (FY) |
2020-04-01 – 2023-03-31
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Keywords | TRPV3 / 好酸球性副鼻腔炎 / 好酸球 / RANTES |
Outline of Final Research Achievements |
Nasal epithelial cells were purified from nasal polyps collected from patients with eosinophilic chronic rhinosinusitis and stimulated with TRPV3 agonist. TRPV3 induced the expression of RANTES from nasal epithelial cells, a chemokine that migrates eosinophils via CCR3 expressed on eosinophils. The expression of RANTES was suppressed when nasal epithelial cells were pre-treated with TRPV3 antagonist and then stimulated with TRPV3 agonist. In addition, intranasal administration of TRPV3 agonist to naive mice on consecutive days resulted in eosinophil infiltration in the nasal mucosa. These results suggest that TRPV3 may induce eosinophil migration in nasal polyps by inducing RANTES production from nasal epithelial cells.
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Free Research Field |
耳鼻咽喉科・頭頸部外科
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Academic Significance and Societal Importance of the Research Achievements |
好酸球性副鼻腔炎の病態には鼻茸上皮細胞、線維芽細胞、肥満細胞など、様々な細胞が関与している。TLR ligands、酸、CysLTなど、様々な因子が引き金となってTRPV3の発現・機能を亢進させ、活性化したTRPV3によるカルシウムイオン流入が、上皮細胞、線維芽細胞、肥満細胞からの炎症因子の放出を誘導するとすれば、TRPV3の活性化による細胞内へのカルシウムイオン流入が、難治性鼻茸の形成メカニズムの中心となっている可能性がある。つまり、TRPV3を制御することができれば、これまでとは全く異なる好酸球性副鼻腔炎の新規治療薬の開発が可能となると考えられる。
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