Son So-Eun, Im Dong-Soon
Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
Department of Biomedical and Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea; Department of Basic Pharmaceutical Sciences, Graduate School, Kyung Hee University, Seoul, 02447, Republic of Korea.
Eur J Pharmacol. 2024 Dec 15;985:177088. doi: 10.1016/j.ejphar.2024.177088. Epub 2024 Oct 31.
G protein-coupled receptor 55 (GPR55) is a lipid-sensing receptor that plays a role as an immune mediator and is primarily upregulated during immune cell activation. There is a lack of knowledge about the role of GPR55 in allergic inflammatory diseases such as atopic dermatitis. The purpose of this study was to investigate the role of GPR55 through the use of its antagonist, CID16020046, in an atopic dermatitis mouse model. It was found that BALB/c mice develop lesions similar to those associated with atopic dermatitis following sensitization and repeated exposure to 1-chloro-2,4-dinitrobenzene (DNCB). It was found that CID16020046 (1 mg/kg, i. p.) alleviated the atopic dermatitis-like symptoms as well as immune dysregulation caused by DNCB. Based on histopathological analysis, CID16020046 reduced ear thickening and mast cell counts in the dermis. CID16020046 decreased DNCB-induced increases in serum IgE levels, as measured using enzyme-linked immunosorbent assays. A significant reduction in lymph node hypertrophy was also observed with CID16020046 as well as significant reductions in CD4 T helper 1 (Th1), Th2, and Th17 cells in the lymph nodes. As a result of the administration of CID16020046, cytokines of Th1 (IFN-γ), Th2 (IL-4 and IL-13), and Th17 (IL-17 A) types were also reduced in the skin and lymph nodes. In conclusion, blocking GPR55 alleviates DNCB-induced atopic dermatitis-like symptoms, suggesting that GPR55 is a potential therapeutic target for allergic inflammatory diseases via immunoregulation.
G蛋白偶联受体55（GPR55）是一种脂质感应受体，作为免疫介质发挥作用，主要在免疫细胞激活过程中上调。目前对于GPR55在特应性皮炎等过敏性炎症性疾病中的作用尚缺乏了解。本研究的目的是通过使用其拮抗剂CID16020046，在特应性皮炎小鼠模型中研究GPR55的作用。研究发现，BALB/c小鼠在致敏并反复接触1-氯-2,4-二硝基苯（DNCB）后会出现与特应性皮炎相关的病变。研究发现，CID16020046（1毫克/千克，腹腔注射）可减轻DNCB引起的特应性皮炎样症状以及免疫失调。基于组织病理学分析，CID16020046可减轻耳部增厚和真皮中肥大细胞计数。使用酶联免疫吸附测定法测量发现，CID16020046可降低DNCB诱导的血清IgE水平升高。还观察到CID16020046可使淋巴结肥大显著减轻，以及淋巴结中CD4辅助性T细胞1（Th1）、Th2和Th17细胞显著减少。由于给予了CID16020046，皮肤和淋巴结中Th1（IFN-γ）、Th2（IL-4和IL-13）和Th17（IL-17A）型细胞因子也减少。总之，阻断GPR55可减轻DNCB诱导的特应性皮炎样症状，表明GPR55通过免疫调节是过敏性炎症性疾病的潜在治疗靶点。
