Zhao Huawei, Zhou Jia, Lu Haimei, Xi Anran, Luo Mengxian, Wang Keer, Lv Hongjie, Wang Huijuan, Wang Ping, Miao Jing, Xu Zhenghao
Department of Pharmacy, Zhejiang University School of Medicine Children's Hospital, Hangzhou, Zhejiang, China.
Laboratory of Rheumatology & Institute of TCM Clinical Basic Medicine, College of Basic Medical Science, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
Int Immunopharmacol. 2022 Jan;102:108388. doi: 10.1016/j.intimp.2021.108388. Epub 2021 Nov 21.
Atopic dermatitis (AD) is a common inflammatory skin disease. This study aims to investigate the effect of azithromycin (AZI) pretreatment, a common macrolide-type antibiotic, on the trimellitic anhydride (TMA) induced AD-like symptoms in mice. AZI (25 mg/kg, once daily, 5 days) was administered intragastrically before the 10-day TMA challenge. AD-like symptoms were assessed by ear thickening, scratching behavior, and pathological or immunofluorescence staining; Cytokines in the skin tissue and serum were measured by cytometric bead array; and the compositions of gut microbiota were assessed by 16S rRNA gene sequencing. AZI pretreatment accelerated the development of ear thickening and enhanced the severity of developed AD-like symptoms. AZI pretreatment promoted the infiltrations of neutrophil-like cells, T cells, and mast cells in ear skin. AZI pretreatment elevated the levels of IL-4, IL-6, and IL-17A in the ear skin of AD model mice, but it increased serum TNF-α and IL-6. AZI-pretreatment increased four gut bacterial genera (Bacteroides, Candidatus_Saccharibacteria_unclassified, Acetatifactor, Firmicutes_unclassified) but depleted three short-chain fatty acids producing gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). AD-associated symptoms were positively associated with skin IL-4 and IL-17A, serum TNF-α, and IL-6, and Acetatifactor, but they negatively correlated to the three decreased gut bacterial genera (Alistipes, Clostridiales_unclassified, Butyricicoccus). Thus, our results demonstrate that AZI exposure deteriorates TMA-induced AD-like symptoms in mice, which is related to the imbalances of gut microbiota and skin/serum cytokines.
特应性皮炎（AD）是一种常见的炎症性皮肤病。本研究旨在探讨常见的大环内酯类抗生素阿奇霉素（AZI）预处理对偏苯三酸酐（TMA）诱导的小鼠AD样症状的影响。在为期10天的TMA激发前，通过灌胃给予AZI（25mg/kg，每日一次，共5天）。通过耳部增厚、抓挠行为以及病理或免疫荧光染色评估AD样症状；通过细胞计数珠阵列检测皮肤组织和血清中的细胞因子；通过16S rRNA基因测序评估肠道微生物群的组成。AZI预处理加速了耳部增厚的发展，并加重了已出现的AD样症状的严重程度。AZI预处理促进了耳部皮肤中嗜中性粒细胞样细胞、T细胞和肥大细胞的浸润。AZI预处理提高了AD模型小鼠耳部皮肤中IL-4、IL-6和IL-17A的水平，但增加了血清TNF-α和IL-6。AZI预处理增加了四个肠道细菌属（拟杆菌属、未分类的候选糖菌属、乙酸杆菌属、未分类的厚壁菌门），但减少了三个产生短链脂肪酸的肠道细菌属（艾氏杆菌属、未分类的梭菌目、丁酸球菌属）。AD相关症状与皮肤IL-4和IL-17A、血清TNF-α和IL-6以及乙酸杆菌属呈正相关，但与三个减少的肠道细菌属（艾氏杆菌属、未分类的梭菌目、丁酸球菌属）呈负相关。因此，我们的结果表明，AZI暴露会恶化TMA诱导的小鼠AD样症状，这与肠道微生物群和皮肤/血清细胞因子的失衡有关。
