Imidazolidinyl urea activates mast cells via MRGPRX2 to induce non-histaminergic allergy.

Abstract

Imidazolidinyl urea (IU) is used as an antimicrobial preservative in cosmetic and pharmaceutical products. IU induces allergic contact dermatitis, however, the mechanism has not yet been elucidated. Mas-related G protein-coupled receptor-X2 (MRGPRX2) triggers drug-induced pseudo-allergic reactions. The aims of this study were to determine whether IU activated mast cells through MRGPRX2 to further trigger contact dermatitis. Wild-type (WT) and KitW-sh/HNihrJaeBsmJNju (MUT) mice were treated with IU to observe its effects on local inflammation and mast cells degranulation in vivo. Laboratory of allergic disease 2 cells were used to detect calcium mobilization and release of inflammatory mediators in vitro. WT mice showed a severe local inflammatory response and contact dermatitis, whereas only slight inflammatory infiltration was observed in MUT mice. Thus, MRGPRX2 mediated the IU-induced activation of mast cells. However, histamine, a typical allergen, was not involved in this process. Tryptase expressed by mast cells was the major non-histaminergic inflammatory mediator of contact dermatitis. IU induced anaphylactic reaction via MRGPRX2 and further triggering non-histaminergic contact dermatitis, which explained why antihistamines are clinically ineffective against some chronic dermatitis.

• Authors: Jiapan Gao, Delu Che, Xueshan Du, Yi Zheng, Huiling Jing, Nan Wang
• Journal: Toxicology research (Toxicol Res (Camb)) Vol. 10 Issue 3 Pg. 467-475 (May 2021) ISSN: 2045-452X [Print] England
• PMID: 34141160 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: [email protected].