Department of Allergy, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400014, PR China.
Department of Allergy, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400014, PR China.
Life Sci. 2021 Feb 1;266:118906. doi: 10.1016/j.lfs.2020.118906. Epub 2020 Dec 16.
The aim of this study was to investigate the role of TRPA1 in the pathogenesis of AD.
The experimental atopic dermatitis (AD)-like skin lesions were established using 2,4-dinitrochlorobenzene (DNCB). Mice were divided into three groups: TRPA1 and WT groups were treated with DNCB dissolved in a 3:1 mixture of acetone and olive oil; the negative control group was treated with 3:1 mixture of acetone and olive oil without DNCB. The treatment lasted for 21 days, after which the animals were sacrificed and their blood, ears and dorsal skin tissue samples were collected for analysis.
Lower dermatitis score, ear thickness, pruritus score, and epidermal hyperplasia were observed in mice in TRPA1 mice compared to the WT group. Besides, lower dermal mast cell infiltration, proinflammatory cytokines, Th2 cytokines and the infiltration of macrophages were observed in the TRPA1 mice compared to the WT group. Furthermore, we demonstrated that TRPA1 antagonist HC-030031 could alleviate AD-like symptoms and reduce the degree of epidermal hyperplasia in mice.
TRPA1 has a crucial role during the AD pathogenesis in mice, thus may be used as a potential new target for treating patients with chronic skin inflammatory disease.
本研究旨在探讨 TRPA1 在 AD 发病机制中的作用。
使用 2,4-二硝基氯苯（DNCB）建立实验性特应性皮炎（AD）样皮肤损伤模型。将小鼠分为三组：TRPA1 和 WT 组用溶解在丙酮和橄榄油 3:1 混合物中的 DNCB 处理；阴性对照组用不含 DNCB 的丙酮和橄榄油 3:1 混合物处理。治疗持续 21 天，然后处死动物，采集血液、耳朵和背部皮肤组织样本进行分析。
与 WT 组相比，TRPA1 组小鼠的皮炎评分、耳部厚度、瘙痒评分和表皮过度增生均较低。此外，与 WT 组相比，TRPA1 组小鼠真皮中的肥大细胞浸润、促炎细胞因子、Th2 细胞因子和巨噬细胞浸润程度较低。此外，我们还证明了 TRPA1 拮抗剂 HC-030031 可减轻 AD 样症状并减少小鼠表皮过度增生的程度。
TRPA1 在小鼠 AD 发病机制中具有重要作用，因此可能成为治疗慢性皮肤炎症性疾病患者的潜在新靶点。
