Department of Dermatology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an 710061, China; School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China; Center for Dermatology Disease, Precision Medical Institute, Xi'an 710000, China.
School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
Int Immunopharmacol. 2022 Sep;110:109063. doi: 10.1016/j.intimp.2022.109063. Epub 2022 Jul 16.
Mast cells (MCs) are main effector cells in chronic spontaneous urticaria (CSU). Both Fc epsilon RI (FcεRΙ)- and MAS-related G coupled receptor-X2 (MRGPRX2)-mediated MC activations affect CSU course. Leukocyte mono-immunoglobulin-like receptor 3 (CD300f) has been shown to regulate FcεRΙ activation. However, no study has verified CD300f is a target to cure CSU. Therefore this study aimed to verify whether clarithromycin (CLA) regulates FcεRΙ- and MRGPRX2-mediated MC activations via CD300f and shows therapeutic effect on CSU. The target of CLA was verification. CLA inhibited FcεRΙ- and MRGPRX2-mediated MC activations were shown in vivo and in vitro. A single-center, self-comparison study was performed, and CLA-treated CSU was investigated in 28 patients who were not sensitive to the third-generation antihistamines. Serum inflammatory mediators in patients before and after CLA administration were analyzed. CLA effectively inhibited type Ι anaphylactic reactions and pseudo-allergic reactions in mice. Moreover, CLA inhibited FcεRΙ- and MRGPRX2-mediated MC signaling pathway activation. Regulatory effects of CLA were decreased significantly after CD300f knockdown. CLA effectively alleviated the symptoms of wheal and itch and reduced serum cytokine levels in patients. CLA negatively regulated FcεRΙ- and MRGPRX2-mediated MC activation via CD300f and showed significant therapeutic effect on CSU.
肥大细胞（MCs）是慢性自发性荨麻疹（CSU）的主要效应细胞。FcεRI（FcεRΙ）和 MAS 相关 G 蛋白偶联受体-X2（MRGPRX2）介导的 MC 激活均影响 CSU 病程。白细胞单免疫球蛋白样受体 3（CD300f）已被证明可调节 FcεRΙ 激活。然而，尚无研究证实 CD300f 是治疗 CSU 的靶点。因此，本研究旨在验证克拉霉素（CLA）是否通过 CD300f 调节 FcεRΙ 和 MRGPRX2 介导的 MC 激活，并对 CSU 具有治疗作用。验证 CLA 的作用靶点。体内和体外实验均表明，CLA 抑制 FcεRΙ 和 MRGPRX2 介导的 MC 激活。进行了一项单中心、自身对照研究，对 28 名对第三代抗组胺药不敏感的 CSU 患者进行了 CLA 治疗。分析了患者 CLA 给药前后的血清炎症介质。CLA 可有效抑制小鼠Ⅰ型过敏反应和假性过敏反应。此外，CLA 抑制 FcεRΙ 和 MRGPRX2 介导的 MC 信号通路激活。CD300f 敲低后，CLA 的调节作用明显下降。CLA 可有效缓解风团和瘙痒症状，降低患者血清细胞因子水平。CLA 通过 CD300f 负调控 FcεRΙ 和 MRGPRX2 介导的 MC 激活，对 CSU 具有显著的治疗作用。
