Elucidation of production mechanism and target proteins of omega-3 fatty acid epoxies that control allergic reactions

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03380
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kono Nozomu 東京大学, 大学院薬学系研究科(薬学部), 准教授 (50451852)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: エポキシ化オメガ3脂肪酸 / PAF-AH2 / マスト細胞 / シトクロムP450

Outline of Final Research Achievements

In mast cells from mice deficient in both Cyp4a12a and Cyp4a12b, IgE/antigen-stimulated activation was markedly attenuated. This attenuation was restored by epoxidized omega-3 fatty acids. TR4 markedly increased Srcin1 promoter activity, and is involved in Srcin1 expression in bone marrow-derived mast cells. These findings indicate that TR4 is essential for Srcin1 expression in mast cells and that epoxy omega-3 fatty acids produced by the Cyp4a12a/b-PAF-AH2 axis regulate Srcin1 expression by suppressing TR4 function.

Free Research Field

脂質生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果によりマスト細胞の活性を制御するエポキシ化オメガ3脂肪酸の産生酵素と作用機構の一端が明らかとなり、生理活性脂肪酸の新たな産生、作用機構を提示できたとともに、アレルギー疾患に対する新たな治療標的を提供できた。