Department of Dermatology, University Hospital Jena, Dermatological Research Laboratory, 07747 Jena, Germany.
Department of Nutritional Biochemistry and Physiology, Institute of Nutritional Science, Friedrich Schiller University, 07743 Jena, Germany.
Int J Mol Sci. 2023 Aug 1;24(15):12325. doi: 10.3390/ijms241512325.
In dermatological research, 2,4-dinitrochlorbenzene (DNCB)-induced atopic dermatitis (AD) is a standard model as it displays many disease-associated characteristics of human AD. However, the reproducibility of the model is challenging due to the lack of information regarding the methodology and the description of the phenotype and endotype of the mimicked disease. In this study, a DNCB-induced mouse model was established with a detailed procedure description and classification of the AD human-like skin type. The disease was induced with 1% DNCB in the sensitization phase and repeated applications of 0.3% and 0.5% DNCB in the challenging phase which led to a mild phenotype of AD eczema. Pathophysiological changes of the dorsal skin were measured: thickening of the epidermis and dermis, altered skin barrier proteins, increased TH1 and TH2 cytokine expression, a shift in polyunsaturated fatty acids, increased pro-resolving and inflammatory mediator formation, and dysregulated inflammation-associated gene expression. A link to type I allergy reactions was evaluated by increased mast cell infiltration into the skin accompanied by elevated IgE and histamine levels in plasma. As expected for mild AD, no systemic inflammation was observed. In conclusion, this experimental setup demonstrates many features of a mild human-like extrinsic AD in murine skin.
在皮肤科研究中,2,4-二硝基氯苯(DNCB)诱导的特应性皮炎(AD)是一种标准模型,因为它显示了许多与人类 AD 相关的疾病特征。然而,由于缺乏关于方法学以及所模拟疾病表型和内型的描述的信息,该模型的重现性具有挑战性。在这项研究中,我们使用详细的程序描述和对类似人类 AD 的皮肤类型的分类,建立了一种 DNCB 诱导的小鼠模型。在致敏阶段使用 1% DNCB 诱导疾病,在挑战阶段重复使用 0.3%和 0.5% DNCB,导致 AD 湿疹的轻度表型。测量背部皮肤的病理生理变化:表皮和真皮增厚,皮肤屏障蛋白改变,TH1 和 TH2 细胞因子表达增加,多不饱和脂肪酸转移,促炎和促修复介质形成增加,以及炎症相关基因表达失调。通过增加皮肤中的肥大细胞浸润,并伴有血浆中 IgE 和组胺水平升高,评估与 I 型过敏反应的联系。与轻度 AD 一致,未观察到全身炎症。总之,该实验方案证明了在小鼠皮肤中存在许多类似人类的轻度特应性皮炎特征。