Nam Yeon Kyung, Kim Mi Hye, Ha In Jin, Yang Woong Mo
Department of Convergence Korean Medical Science, College of Korean Medicine, Kyung Hee University, Seoul 02447, Korea.
Korean Medicine Clinical Trial Center, Kyung Hee University Korean Medicine Hospital, Kyung Hee University, Seoul 02454, Korea.
Int J Mol Sci. 2021 Feb 26;22(5):2359. doi: 10.3390/ijms22052359.
Atopic dermatitis (AD) is a chronic cutaneous disorder that is characterized by severe eczematous inflammation, swelling, and lichenification. Activation of T helper (Th)-22 cells by allergens leads to epidermal hyperplasia with hyperkeratosis at the chronic phase of AD. Derma-Hc is composed of five natural herbs with anti-AD effects, such as BUNGE, Briq., Fabr., Diels, L. In this study, the ameliorative effect of Derma-Hc on cutaneous lichenification in 2,4-dinitrochlorobenzne (DNCB)-induced AD was investigated. The dorsal skin of mice was sensitized with DNCB to induce AD-like skin lesions. The dermatitis score and frequency of scratching were evaluated. Thickness of epidermis and dermis was measured by staining with H&E. In addition, infiltration of the mast cell was observed by staining with toluidine blue. Then, desmosomal cadherin, DSC1 was examined by immunofluorescence. Pathological mechanisms involved in lichenification were analyzed in AD-like skin lesions and TNF-α + IFN-γ-treated with human keratinocytes including keratinocyte differentiation genes and JAK1-STAT3 signaling pathway with IL-22 by RT-PCR and western blotting. Topical treatment of Derma-Hc improved AD-like symptoms such as dryness, edema and lichenefication and decreased the number of scratches. Histopathological analysis demonstrated that Derma-Hc significantly inhibited epidermal hyperplasia, hyperkeratosis, and mast cells infiltration. In addition, the level of DSC1 was highly expressed in the epidermis by Derma-Hc. Moreover, mRNA expression level of FLG, an epidermal differentiation complex gene, was recovered by Derma-Hc treatment. KLK5 and KLK7 were markedly reduced to normalize keratinocyte differentiation in dorsal skin tissues and human keratinocytes. On the other hand, Derma-Hc restored expression level of SPINK5. In addition, Derma-Hc inhibited IL-22 via the blockade of JAK1-STAT3 signal pathway. Taken together, Derma-Hc, a natural herbal formula, regulated keratinocyte differentiation and inhibited epidermal hyperplasia with hyperkeratosis. Therefore, Derma-Hc could be a promising candidate for treating chronic AD through modulating signaling of IL-22-associated skin lichenification.
特应性皮炎（AD）是一种慢性皮肤疾病，其特征为严重的湿疹性炎症、肿胀和苔藓化。在AD的慢性期，变应原激活辅助性T（Th）-22细胞会导致伴有角化过度的表皮增生。Derma-Hc由五种具有抗AD作用的天然草药组成，如[此处草药名称未完整给出，无法准确翻译]。在本研究中，研究了Derma-Hc对2,4-二硝基氯苯（DNCB）诱导的AD皮肤苔藓化的改善作用。用DNCB使小鼠背部皮肤致敏以诱导AD样皮肤损伤。评估皮炎评分和搔抓频率。通过苏木精-伊红（H&E）染色测量表皮和真皮的厚度。此外，通过甲苯胺蓝染色观察肥大细胞的浸润情况。然后，通过免疫荧光检测桥粒钙黏蛋白DSC1。在AD样皮肤损伤以及用肿瘤坏死因子-α + 干扰素-γ处理的人角质形成细胞中，通过逆转录-聚合酶链反应（RT-PCR）和蛋白质印迹法分析与苔藓化相关的病理机制，包括角质形成细胞分化基因和具有白细胞介素-22的JAK1-STAT3信号通路。局部应用Derma-Hc改善了AD样症状，如干燥、水肿和苔藓化，并减少了搔抓次数。组织病理学分析表明，Derma-Hc显著抑制表皮增生、角化过度和肥大细胞浸润。此外，Derma-Hc使表皮中DSC1的水平高表达。而且，通过Derma-Hc处理可使表皮分化复合基因FLG的mRNA表达水平恢复。组织激肽释放酶5（KLK5）和组织激肽释放酶7（KLK7）明显降低，以使背部皮肤组织和人角质形成细胞中的角质形成细胞分化正常化。另一方面，Derma-Hc恢复了丝氨酸蛋白酶抑制剂Kazal 5型（SPINK5）的表达水平。此外，Derma-Hc通过阻断JAK1-STAT3信号通路抑制白细胞介素-22。综上所述，天然草药配方Derma-Hc调节角质形成细胞分化并抑制伴有角化过度的表皮增生。因此，Derma-Hc可能是通过调节白细胞介素-22相关皮肤苔藓化信号来治疗慢性AD的有前景的候选药物。
