Development of a novel treatment for eosinophilic sinusitis by controlling the fibrinolytic system.
| Project/Area Number |
20K09686
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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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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | University of Fukui |
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Principal Investigator |
Takabayashi Tetsuji 福井大学, 学術研究院医学系部門(附属病院部), 講師 (70397272)
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| Co-Investigator(Kenkyū-buntansha) |
加藤 幸宣 福井大学, 学術研究院医学系部門(附属病院部), 助教 (00748981)
吉田 加奈子 福井大学, 学術研究院医学系部門(附属病院部), 特命助教 (00773706)
坂下 雅文 福井大学, 学術研究院医学系部門(附属病院部), 講師 (40555455)
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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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 好酸球性副鼻腔炎 / フィブリン / 組織型プラスミノーゲンアクチベーター / 好酸球 / M2マクロファージ / 鼻茸 / 凝固系 / 線溶系 / 組織型プラスミノーゲンアクチベータ / 慢性副鼻腔炎 / tPA / フィブリン網 / 肥満細胞 |
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| Outline of Research at the Start |
好酸球性副鼻腔炎における治療の成否は難治性で易再発性の鼻茸をいかにコントロールするかにかかっている。しかし現時点で決定的な治療法はない。申請者はこれまでに鼻・副鼻腔粘膜における過剰なフィブリン網の沈着が浮腫を遷延させ、鼻茸形成に関与することを明らかにした。本研究では、組織内で過剰に形成されたフィブリン網の合成、および分解に重要な、凝固・線溶系の制御機構、またこれらに対する肥満細胞の関与、そして腸内細菌が鼻粘膜における線溶系に与える影響について、摘出標本、培養細胞、モデルマウスを用いて検討し、新規治療法の開発につなげる。
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| Outline of Final Research Achievements |
In eosinophilic sinusitis, it is of great importance to understand the mechanism of nasal mushroom formation, and our previous studies have shown that excessive fibrin network formation in the nasal sinus mucosa is responsible for the prolonged oedema. In the present study, we have demonstrated the involvement of M2 macrophages infiltrating the nasal sinus mucosa in the enhancement of the coagulation system. Furthermore, Nasal NO was significantly decreased in eosinophilic sinusitis and could be a biomarker for the condition, or could provide more useful information than endoscopic findings when deciding whether to continue or reduce the use of biologics.
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| Academic Significance and Societal Importance of the Research Achievements |
好酸球性副鼻腔炎は難治性の疾患で指定難病にも登録されている。鼻副鼻腔粘膜の浮腫の遷延によって形成される鼻茸は鼻腔に特徴的な病変で同じ気道の２型炎症性疾患である気管支喘息やアトピー性皮膚炎患者においてこのような病変の局所での形成は認められない。好酸球性副鼻腔炎おいて鼻茸の形成メカニズムを解明することは非常に重要であるが、本結果は凝固線溶系の不均衡を解除し新規治療法の開発に有用であると考えられた。
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Report
(4 results)
Research Products
(28 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] 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] Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis2020
Author(s)
Oka A, Ninomiya T, Fujiwara T, Takao S, Sato Y, Gion Y, Minoura A, Haruna SI, Yoshida N, Sakuma Y, Izuhara K, Ono J, Taniguchi M, Haruna T, Higaki T, Kariya S, Koyama T, Takabayashi T, Imoto Y, Sakashita M, Kidoguchi M, Nishizaki K, Fujieda S, Okano M.
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Journal Title
Allergology International
Volume: 69
Issue: 3
Pages: 417-423
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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[Journal Article] Association between the NOS2 pentanucleotide repeat polymorphism and risk of postoperative recurrence of chronic rhinosinusitis with nasal polyps in a Japanese population.2020
Author(s)
Kidoguchi M, Yoshida K, Noguchi E, Nakamura T, Morii W, Haruna T, Okano M, Yamashita Y, Haruna S, Hasegawa M, Yoshida N, Ninomiya T, Imoto Y, Sakashita M, Takabayashi T, Fujieda S.
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Journal Title
Allergology International
Volume: 69(4)
Issue: 4
Pages: 619-621
DOI
NAID
Related Report
Peer Reviewed / Open Access
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