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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Project Status |
Completed (Fiscal Year 2022)
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Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | TRPV3 / 好酸球性副鼻腔炎 / 好酸球 / RANTES |
Outline of Research at the Start |
本研究では好酸球性副鼻腔炎におけるTRPV3の機能解析と新たな治療戦略を目的とする。In vitroでは、様々な細胞株におけるTRPV3を介したカルシウム動態から、TRPV3を活性化させる因子、TRPV3によって誘導される因子を解析する。In vivoでは好酸球性炎症モデルマウスを作製し、TRPV3 agonistやTRPV3 antagonistを用いて好酸球性炎症への関与を検証する。TRPV3を中心とした好酸球性副鼻腔炎の病態解明により、新規治療薬・根治治療の可能性を追求する。
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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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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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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis2022
Author(s)
Imoto Yoshimasa、Ueki Shigeharu、Kato Yukinori、Yoshida Kanako、Morikawa Taiyo、Kimura Yukihiro、Kidoguchi Masanori、Tsutsumiuchi Toshiki、Koyama Keisuke、Adachi Naoto、Ito Yumi、Ogi Kazuhiro、Sakashita Masafumi、Yamada Takechiyo、Schleimer Robert P.、Takabayashi Tetsuji、Fujieda Shigeharu
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Journal Title
Frontiers in Pharmacology
Volume: 12
Pages: 793607-793607
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] 2.論文標題 Involvement of activation of mast cells via IgE signaling and epithelial cell-derived cytokines in the pathogenesis of pollen-food allergy syndrome in a novel murine model2021
Author(s)
Kato, Y., Morikawa, T., Kato, E., Yoshida, K., Imoto, Y., Sakashita, M., Osawa, Y., Takabayashi, T., Kubo, M., Miura, K., Noguchi, E., Fujieda, S.
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Journal Title
The Journal of Immunology
Volume: 206
Issue: 12
Pages: 1-12
DOI
Related Report
Peer Reviewed
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[Journal Article] Comparison of sensitization and prevalence of Japanese cedar pollen and mite-induced perennial allergic rhinitis between 2006 and 2016 in hospital workers in Japan2021
Author(s)
Sakashita M, Tsutsumiuchi T, Kubo S, Tokunaga T, Takabayashi T, Imoto Y, Kato Y, Yoshida K, Kimura Y, Kato Y, Kanno M, Ogi K, Okamoto M, Narita N, Fujieda S.
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Journal Title
Allergology International
Volume: 70
Issue: 1
Pages: 89-95
DOI
NAID
ISSN
1323-8930, 1440-1592
Related Report
Peer Reviewed / Open Access
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[Journal Article] Enhanced 15-Lipoxygenase 1 Production is Related to Periostin Expression and Eosinophil Recruitment in Eosinophilic Chronic Rhinosinusitis2020
Author(s)
Imoto Y, Takabayashi T, Sakashita M, Kato Y, Yoshida K, Kidoguchi M, Koyama K, Adachi N, Kimura Y, Ogi K, Ito Y, Kanno M, Okamoto M, Narita N, Fujieda S.
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Journal Title
Biomolecules
Volume: 18;10(11)
Issue: 11
Pages: 1568-1568
DOI
Related Report
Peer Reviewed / Open Access
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