Elucidation of leukotriene B4 receptor 1, BLT1-dependent immune response by dendritic cells and neutrophils

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K19032
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Kumamoto University (2016); Juntendo University (2015)
• Principal Investigator: KOGA TOMOAKI 熊本大学, 大学院先導機構, 助教 (30615092)
• Co-Investigator(Renkei-kenkyūsha): Yokomizo Takehiko 順天堂大学, 医学部・生化学第一講座, 教授 (60302840)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 生理活性脂質 / 好中球 / 樹状細胞 / GPCR / ロイコトリエンB4 / BLT1

Outline of Final Research Achievements

In the present study, we investigated the role of LTB4-BLT1 axis in neutrophils and dendritic cells. We found that BLT1 interacts with receptor for advanced glycation end products (RAGE), which is important receptor for the regulation of various chronic inflammatory diseases including diabetes, atherosclerosis, Alzheimer's diseases and etc. We also showed that RAGE enhances LTB4-BLT1-dependent neutrophil migration in vitro and in vivo through the activation of MEK-ERK signaling pathway. RAGE is known to be up-regulated by aging, so it might be possible that BLT1 signaling is exaggerated by aging through RAGE induction in vivo. If we can inhibit RAGE, we might also inhibit LTB4-BLT1 signaling, and subsequent infiltration of neutrophils into inflammatory area. We therefore propose RAGE as a novel therapeutic target for various inflammatory diseases by targeting LTB4-BLT1 signaling.

Free Research Field

脂質免疫学