2022 Fiscal Year Final Research Report
Basic research on the effects of eicosapentaenoic acid metabolites on upper airway inflammation
| Project/Area Number |
20K09754
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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 | Shiga University of Medical Science |
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Principal Investigator |
TOJIMA Ichiro 滋賀医科大学, 医学部, 講師 (80567347)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 17,18-EpETE / 17,18-diHETE / ILC2 / IL-33 / eosinophil / airway epithelial cells / TNF-α / neutrophil |
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| Outline of Final Research Achievements |
17,18-EpETE and its metabolites 17,18-diHETE attenuated human ILC2-derived productions of IL-5 and IL-13 in response to IL-33 through the inhibition of GATA-3. These anti-inflammatory effects on ILC2s may be mediated by the receptors of GPR40 and PPARγ. Intranasal administration of 17,18-EpETE and 17,18-diHETE attenuated IL-33-induced eosinophil infiltrations and mucus productions in mouse nasal epithelium, and the productions of IL-5/IL-13 in lung tissues and BALs.
17,18-EpETE attenuated human airway epithelial cell-derived productions of IL-6, IL-8, and MUC5AC in response to TNF-α. These effects may be mediated by GPR40. Intranasal or intraperitoneal administration of 17,18-EpETE attenuated lipopolysaccharide-induced neutrophil infiltrations and mucus productions in mouse nasal epithelium. Inflammatory cytokine/chemokine productions in lung tissues and BALs was also inhibited. These effects of 17,18-EpETE might apply for eosinophilic and neutrophilic airway inflammatory disorders.
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| Free Research Field |
上気道炎症
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| Academic Significance and Societal Importance of the Research Achievements |
17,18-EpETEやその代謝物17,18-diHETEは、ヒト生体内で合成される脂質代謝物であるため、安全な治療手段となる可能性を秘めている。今回のわれわれの結果から、17,18-EpETEや17,18-diHETEはIL-33で刺激したヒトILC2からの2型サイトカイン産生を抑制し、これらの点鼻投与はマウスの上気道好酸球炎症を抑制した。またTNF-αで刺激したヒト気管支上皮細胞からの炎症性メディエーターの産生も抑制し、マウスの上気道好中球性炎症に対しても抑制作用を示した。17,18-EpETEは、好酸球性鼻副鼻腔炎や好中球性の上気道炎症などに対する安全な新規治療法となる可能性がある。
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