Laboratory of Cutaneous Aging and Hair Research, Clinical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
Institute of Human Environment Interface Biology, Seoul National University, Seoul, Republic of Korea.
Sci Rep. 2020 May 21;10(1):8417. doi: 10.1038/s41598-020-65502-2.
The main factors involved in the pathogenesis of atopic dermatitis (AD) are skin barrier abnormality, allergy/immunology, and pruritus. Considering how oxidative stress influences these factors, antioxidant agents may be effective candidates in the treatment of AD. To evaluate the effect of Caffeoyl-Pro-His amide (CA-PH), an antioxidant agent, on 2,4-dinitrochlorobenzene (DNCB)-induced AD-like phenotypes in BALB/c mice. Topical sensitization and challenge by DNCB were performed on the dorsal skin of BALB/c mice to induce AD-like cutaneous lesions, phenotypes, and immunologic response. CA-PH was applied topically for 2 weeks to assess its effects on DNCB-induced AD-like phenotypes. As a result, CA-PH relieved DNCB-induced AD-like phenotypes quantified by dermatitis severity score, scratching duration, and trans-epidermal water loss. Histopathological analysis showed that CA-PH decreased epidermal thickening, the number of mast cells, and eosinophil infiltration in dermis. Immunohistochemical staining revealed that CA-PH recovered skin barrier-related proteins: filaggrin, involucrin, and loricrin. As for the immunologic aspects, CA-PH treatment lowered mRNA or protein levels of interleukin (IL)-4, IL-6, IL-17a, IL-1b, IL-31, and IL-33 levels and thymic stromal lymphopoietin (TSLP) levels in cutaneous tissue, reducing the DNCB-induced serum IgE level elevation. In conclusion, topical CA-PH may be a therapeutic option for the treatment of AD.
特应性皮炎(AD)发病机制中的主要因素包括皮肤屏障异常、过敏/免疫学和瘙痒。考虑到氧化应激如何影响这些因素,抗氧化剂可能是 AD 治疗的有效候选药物。评估抗氧化剂咖啡酰脯氨酸酰胺(CA-PH)对 2,4-二硝基氯苯(DNCB)诱导的 BALB/c 小鼠 AD 样表型的影响。通过 DNCB 对 BALB/c 小鼠的背部皮肤进行局部致敏和挑战,以诱导 AD 样皮肤损伤、表型和免疫反应。局部应用 CA-PH 2 周,评估其对 DNCB 诱导的 AD 样表型的影响。结果表明,CA-PH 缓解了 DNCB 诱导的 AD 样表型,通过皮炎严重程度评分、搔抓持续时间和经表皮水分流失进行量化。组织病理学分析显示 CA-PH 减少了表皮增厚、真皮中的肥大细胞和嗜酸性粒细胞浸润。免疫组织化学染色显示 CA-PH 恢复了皮肤屏障相关蛋白:丝聚蛋白、兜甲蛋白和板层素。至于免疫学方面,CA-PH 治疗降低了皮肤组织中白细胞介素(IL)-4、IL-6、IL-17a、IL-1b、IL-31 和 IL-33 以及胸腺基质淋巴细胞生成素(TSLP)的 mRNA 或蛋白水平,降低了 DNCB 诱导的血清 IgE 水平升高。总之,局部 CA-PH 可能是 AD 治疗的一种选择。