Jin Jiang, Chen Xue, Zhao Yan, Jia Jun, Zhang Jianzhong
Department of Dermatology, Peking University People's Hospital, Beijing 100044, China.
Beijing Da Xue Xue Bao Yi Xue Ban. 2024 Oct 18;56(5):756-762. doi: 10.19723/j.issn.1671-167X.2024.05.002.
To investigate the effect of interleukin-25 (IL-25) on ovalbumin (OVA) induced atopic dermatitis of mice, and the significance of regulating IL-25.
In this study, 90 healthy male 6-week-old specific pathogen free (SPF) BALB/c mice were divided into 6 groups (15 in each group): ① subcutaneous injection of phosphate buffered saline (PBS) group (normal control group); ② subcutaneous injection of mouse IL-25 group (IL-25 group); ③ subcutaneous injection of anti-mouse IL-25 monoclonal antibody (anti-IL-25 group), each group received subcutaneous injection once a day for 1 week, 2 weeks apart, repeated daily subcutaneous injections for 1 week, 2 weeks apart, and repeated daily subcutaneous injections for 1 week, for a total of 7 weeks; ④ OVA treated group (model group); ⑤ OVA treated and IL-25 subcutaneous injection group (IL-25 treated dermatitis group); ⑥ OVA treated and anti-mouse IL-25 monoclonal antibody injection group (anti-IL-25 treated dermatitis group). The ⑤ and ⑥ groups in the process of treatment with OVA, IL-25 or anti-IL-25 antibody were given in the same way as the ② and ③ groups. Scratching behavior and skin performance of the mice were recorded during the seven-week-treatment. Twenty four hours after the final treatment, blood was taken from the mouse heart, and the serum was separated to detect the total IgE, IL-4, IL-5, IL-13, . The skin samples of the treatment sites were used for hematoxylin-eosin (HE) staining, immunohistochemistry, real-time PCR and Western blot detections. A single factor (ANOVA) analysis of variance was used to compare the differences in various indicators between the groups.
The frequency of scratches in the IL-25 treated dermatitis group was higher than that in the model group, and the scratching behavior of the anti-IL-25 treated dermatitis group was significantly lower than that in the model group. The appearance of atopic dermatitis, thickening of the epidermis and the degree of dermal inflammation in the IL-25 treated dermatitis group were more serious than those in the model group and the anti-IL-25 treated dermatitis group. The levels of serum IgE, IL-4, IL-5, and IL-13 in the IL-25 treated dermatitis group were significantly higher than that in the model group and the anti-IL-25 treated dermatitis group. There were significantly more CD4 T cells in the dermis of IL-25 treated dermatitis group than that in the anti-IL-25 treated dermatitis group. The expression levels of filaggrin and defensin β2 proteins in the IL-25 treated dermatitis group were significantly lower than those in the model group and the anti-IL-25 treated dermatitis group.
In the OVA induced atopic dermatitis mice model, IL-25 can significantly promote the damage of the epidermal barrier function and aggravate the OVA-induced dermatitis. Antagonizing IL-25 can alleviate OVA induced dermatitis to a certain extent.
探讨白细胞介素-25（IL-25）对卵清蛋白（OVA）诱导的小鼠特应性皮炎的影响以及调节IL-25的意义。
本研究将90只6周龄健康雄性无特定病原体（SPF）BALB/c小鼠分为6组（每组15只）：①皮下注射磷酸盐缓冲液（PBS）组（正常对照组）；②皮下注射小鼠IL-25组（IL-25组）；③皮下注射抗小鼠IL-25单克隆抗体组（抗IL-25组），每组每天皮下注射1次，共1周，间隔2周，再重复每天皮下注射1周，间隔2周，再重复每天皮下注射1周，共7周；④OVA处理组（模型组）；⑤OVA处理并皮下注射IL-25组（IL-25治疗性皮炎组）；⑥OVA处理并注射抗小鼠IL-25单克隆抗体组（抗IL-25治疗性皮炎组）。⑤和⑥组在OVA、IL-25或抗IL-25抗体治疗过程中，给药方式同②和③组。在7周治疗期间记录小鼠的搔抓行为和皮肤表现。末次治疗24小时后，从小鼠心脏采血，分离血清检测总IgE、IL-4、IL-5、IL-13等。取治疗部位皮肤样本进行苏木精-伊红（HE）染色、免疫组化、实时荧光定量PCR和蛋白质免疫印迹检测。采用单因素方差分析（ANOVA）比较各组各项指标的差异。
IL-25治疗性皮炎组的搔抓频率高于模型组，抗IL-25治疗性皮炎组的搔抓行为明显低于模型组。IL-25治疗性皮炎组特应性皮炎的外观、表皮增厚和真皮炎症程度比模型组和抗IL-25治疗性皮炎组更严重。IL-25治疗性皮炎组血清IgE、IL-4、IL-5和IL-13水平明显高于模型组和抗IL-25治疗性皮炎组。IL-25治疗性皮炎组真皮中CD4+T细胞明显多于抗IL-25治疗性皮炎组。IL-25治疗性皮炎组中丝聚合蛋白和防御素β2蛋白的表达水平明显低于模型组和抗IL-25治疗性皮炎组。
在OVA诱导的小鼠特应性皮炎模型中，IL-25可显著促进表皮屏障功能损伤，加重OVA诱导的性皮炎。拮抗IL-25可在一定程度上减轻OVA诱导的性皮炎。
