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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.
摘要：
咪唑烷基脲(IU)在化妆品和药物产品中用作抗微生物防腐剂。IU诱导过敏性接触性皮炎，然而,机制尚未阐明。Mas相关G蛋白偶联受体X2(MRGPRX2)引发药物诱导的假性过敏反应.本研究的目的是确定IU是否通过MRGPRX2激活肥大细胞进一步引发接触性皮炎。野生型（WT）和KitW-sh/HNihrJaeBsmJNju（MUT）小鼠用IU处理，观察其对体内局部炎症和肥大细胞脱颗粒的影响。变应性疾病2细胞的实验室用于检测钙动员和体外炎症介质的释放。WT小鼠表现出严重的局部炎症反应和接触性皮炎，而在MUT小鼠中仅观察到轻微的炎症浸润。因此，MRGPRX2介导IU诱导的肥大细胞活化。然而,组胺,一种典型的过敏原,没有参与这个过程。肥大细胞表达的类胰蛋白酶是接触性皮炎的主要非组胺能炎症介质。IU通过MRGPRX2诱导过敏反应，并进一步引发非组胺能接触性皮炎，这解释了为什么抗组胺药在临床上对一些慢性皮炎无效。
