2022 Fiscal Year Final Research Report
Molecular mechanisms and physiological significance of short chain fatty acid- and polyunsaturated fatty acid-mediated regulation of mast cell function
| Project/Area Number |
20H02939
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 38050:Food sciences-related
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
Nishiyama Chiharu 東京理科大学, 先進工学部生命システム工学科, 教授 (20327836)
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| Co-Investigator(Kenkyū-buntansha) |
八代 拓也 東京理科大学, 基礎工学部生物工学科, 講師 (00726482)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Keywords | 短鎖脂肪酸 / マスト細胞 / 多価不飽和脂肪酸 / PGE2 / Gタンパク質共役型受容体 / GPR109A / IgE / アナフィラキシー |
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| Outline of Final Research Achievements |
Short chain fatty acids, including butyrate and propionate, are produced by commensal bacteria during fermentation of dietary fibers in the intestine. Almost SCFAs excepting for acetate significantly inhibited IgE-dependent activation of mast cells. In the present study, we analyzed mechanisms of anti-allergic effects of SCFAs and found that SCFAs exerted anti-allergic effects with two different roles; briefly, one is a HDAC inhibition activity and the other is as a ligand of GPR109A. We also revealed that the PGE2-EP3 pathway is involved in the anti-allergic effects of SCFAs and that administration of nicotinic acid, which activates GPR109A, suppressed IgE-induced passive anaphylaxis in mice.
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| Free Research Field |
免疫・アレルギー学、分子栄養学、食品機能学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、SCFAがIgE依存的マスト細胞活性化を抑制する仕組みをin vivo、in vitro実験系を用いて明らかにし、罹患者数が多く且つ近年増加の一途を辿るアレルギー疾患の緩和に、日々摂取する食品成分が影響を及ぼすことを証明した。アスピリンやインドメタシンがその効果を阻害することや、ビタミンB3であるニコチン酸にもアレルギー抑制効果があることなど、非ステロイド性抗炎症薬やサプリメントの作用が生体レベルで明らかにされた。マスト細胞上のGPR109Aが果たす役割やSCFAとプロスタノイドの関係など、アレルギー疾患の病態緩和や予防を目指す次なる研究課題の提案に繋がった。
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