Receptors that recognize lipoquality

2019 Fiscal Year Final Research Report

• Project Area: Quality of lipids in biological systems
• Project/Area Number: 15H05904
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Juntendo University
• Principal Investigator: Yokomizo Takehiko 順天堂大学, 医学(系)研究科(研究院), 教授 (60302840)
• Co-Investigator(Kenkyū-buntansha): 小林 雄一 明治大学, 研究・知財戦略機構, 研究推進員(客員研究員) (90153650)
• Project Period (FY): 2015-06-29 – 2020-03-31
• Keywords: ロイコトリエン / プロスタグランジン / アラキドン酸 / オメガ3脂肪酸 / アレルギー / バリア機能 / 上皮修復

Outline of Final Research Achievements

BLT1, a receptor for leukotriene B4, is expressed in M2 macrophages and exacerbates pathological angiogenesis in age-related macular degeneration (AMD) and allergic conjunctivitis in mice. BLT2, a receptor for leukotriene B4, 12-hydroxyheptadecatrienoic acid, and other fatty acids, is expressed in the epithelium of the skin and cornea and plays positive roles in maintenance and repair of epithelial barrier function. In addition, BLT2 was found to be expressed in pulmonary vascular endothelial cells and prevented individual death due to acute lung injury caused by bacterial toxins including pneumolysis. A diet rich in omega-3 fatty acids inhibited allergic inflammatory responses by competing the omega-6 fatty acid metabolic pathways. Total organic synthesis methods for novel lipid mediators derived from omega-3 fatty acids were established.

Free Research Field

脂質生物学

Academic Significance and Societal Importance of the Research Achievements

近年、食生活の西欧化に伴い、魚油に豊富に含まれるオメガ3脂肪酸の摂取が減少傾向にあり、これがアレルギー性疾患の患者の増加につながっているする説がある。しかしながらオメガ3脂肪酸摂取が引き起こす体内の脂質の質(リポクオリティ)の変化や、それらに由来する生理活性脂質を認識する受容体の分子機構は明らかでは無かった。本研究で得られたオメガ3脂肪酸とオメガ6脂肪酸の代謝の拮抗はオメガ3脂肪酸の効果の理論的な裏付けとなる。また、BLT1受容体抑制やBLT2受容体活性化による炎症・アレルギー疾患の抑制効果は、新規創薬の理論的根拠となる。