2. Academic Validation
  3. Clarithromycin-treated chronic spontaneous urticaria with the negative regulation of FcεRΙ and MRGPRX2 activation via CD300f

Clarithromycin-treated chronic spontaneous urticaria with the negative regulation of FcεRΙ and MRGPRX2 activation via CD300f

  • Int Immunopharmacol. 2022 Sep;110:109063. doi: 10.1016/j.intimp.2022.109063.
Delu Che 1,  Tao Zhang 2,  Tianxiao Zhang 3,  Yi Zheng 4,  Yajing Hou 2,  Songmei Geng 5,  Langchong He 6
Affiliations

Affiliations

  • 1 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.
  • 2 School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China.
  • 3 School of Public Health, Xi'an Jiaotong University, Xi'an 710061, China.
  • 4 Department of Dermatology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an 710061, China.
  • 5 Department of Dermatology, Xi'an Jiaotong University Second Affiliated Hospital, Xi'an 710061, China; Center for Dermatology Disease, Precision Medical Institute, Xi'an 710000, China. Electronic address: gsm312@yahoo.com.
  • 6 School of Pharmacy, Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: helc@mail.xjtu.edu.cn.
PMID: 35853276 DOI: 10.1016/j.intimp.2022.109063
Abstract

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.

Keywords

Chronic spontaneous urticarial; Clarithromycin; Leukocyte mono-immunoglobulin-like receptor 3; Mast cell; Negatively regulation.

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