Department of Biochemistry, Graduate School of Medicine, Juntendo University, Tokyo, Japan.
Institute of Microbial Chemistry, Tokyo, Japan.
Immunol Rev. 2023 Aug;317(1):30-41. doi: 10.1111/imr.13196. Epub 2023 Mar 13.
Leukotriene B (LTB ) was recognized as an arachidonate-derived chemotactic factor for inflammatory cells and an important drug target even before the molecular identification of its receptors. We cloned the high- and low-affinity LTB receptors, BLT1 and BLT2, respectively, and examined their functions by generating and studying gene-targeted mice. BLT1 is involved in the pathogenesis of various inflammatory and immune diseases, including asthma, psoriasis, contact dermatitis, allergic conjunctivitis, age-related macular degeneration, and immune complex-mediated glomerulonephritis. Meanwhile, BLT2 is a high-affinity receptor for 12-hydroxyheptadecatrienoic acid, which is involved in the maintenance of dermal and intestinal barrier function, and the acceleration of skin and corneal wound healing. Thus, BLT1 antagonists and BLT2 agonists are promising candidates in the treatment of inflammatory diseases.
白三烯 B（LTB）在其受体的分子鉴定之前，就被认为是一种花生四烯酸衍生的趋化因子，是炎症细胞的重要药物靶点。我们分别克隆了高亲和力和低亲和力的 LTB 受体，BLT1 和 BLT2，并通过生成和研究基因靶向小鼠来研究其功能。BLT1 参与了各种炎症和免疫性疾病的发病机制，包括哮喘、银屑病、接触性皮炎、过敏性结膜炎、年龄相关性黄斑变性和免疫复合物介导的肾小球肾炎。同时，BLT2 是 12-羟基十七碳三烯酸的高亲和力受体，参与维持皮肤和肠道屏障功能，并加速皮肤和角膜伤口愈合。因此，BLT1 拮抗剂和 BLT2 激动剂是治疗炎症性疾病的有前途的候选药物。
