Inhibitory effects of isoliquiritin on an atopic dermatitis model through the CD177/JAK2/STAT pathway in vitro and in vivo.
Inhibitory effects of isoliquiritin on an atopic dermatitis model through the CD177/JAK2/STAT pathway in vitro and in vivo.
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DOI：
10.21037/atm-22-3989
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发表时间：
2022-09
影响因子：
--
通讯作者：
Yan, Fenggen
中科院分区：
文献类型：
--
作者：
Wu, Qing;Mo, Xiumei;Lin, Ying;Liu, Junfeng;Ye, Siqi;Zhang, Yu;Fan, Xingxing;Chen, Dacan;Yan, Fenggen
特应性皮炎（AD）是一种以皮肤免疫细胞增殖和激活为特征的复杂炎症性皮肤病。异甘草素（Isoliquiritin，ISO）是从光叶甘草中分离得到的有效成分。本研究旨在测试ISO对AD的治疗潜力，并验证其潜在的分子机制。本研究探讨了ISO在体外（佛波醇-12-肉豆蔻酸酯-13-乙酸酯和钙离子载体A23187刺激的HMC 1.1细胞）和体内（1-氯-2，4-二硝基氯苯诱导的AD样小鼠模型）抗AD的潜在作用和可能的潜在机制。ISO剂量依赖性地抑制HMC1.1细胞的活力。ISO可抑制HMC1.1细胞分泌促炎因子IL-6和IL-8，并诱导细胞凋亡。ISO抑制CD 177、JAK 2、STAT 1、STAT 3和STAT 5的磷酸化，上调BAX和切割的caspase-3的蛋白表达。ISO管理显着减少浸润的免疫细胞（肥大细胞，嗜酸性粒细胞）在皮肤病变。同时，ISO治疗减轻了皮肤病变的形成，并影响其他AD症状（表皮和真皮厚度，耳水肿，淋巴结重量，脾指数，皮炎评分），但增加了体内胸腺指数，并下调IL-4，IL-6，IgE和胸腺基质淋巴细胞生成素（TSLP）的表达。总的来说，我们的研究结果表明，ISO给药通过抑制炎症和通过CD 177/JAK 2/STAT信号通路增强免疫调节来减少皮肤病变的形成。
Atopic dermatitis (AD) is a complex inflammatory skin condition characterized by the proliferation and activation of immune cells in skin. Isoliquiritin (ISO) is an active component purified from Glycyrrhiza glabra. This study aimed to test the therapeutic potential of ISO for AD and verify its potential molecular mechanism. This study investigated the potential effects and possible underlying mechanisms of ISO against AD in vitro (HMC1.1 cells stimulated by phorbol-12-myristate-13-acetate and calcium ionophore A23187) and in vivo (AD-like mouse model induced by 1-chloro-2,4-dinitrochlorobenzene). ISO dose-dependently suppressed the viability of HMC1.1 cells. ISO inhibited the secretion of the proinflammatory factors IL-6 and IL-8 and induced the apoptosis of HMC1.1 cells. ISO suppressed the phosphorylation of CD177, JAK2, STAT1, STAT3, and STAT5, and upregulated the protein expression of BAX and cleaved caspase-3 in vitro. ISO administration markedly diminished the infiltration of immune cells (mast cells, eosinophils) in cutaneous lesions. Simultaneously, ISO treatment alleviated the formation of skin lesions and affected other AD symptoms (thickness of the epidermis and dermis, ear edema, lymph node weight, spleen index, dermatitis score) but increased the thymus index in vivo, and downregulated expression of IL-4, IL-6, IgE, and thymic stromal lymphopoietin (TSLP). Collectively, our findings showed that ISO administration decreased skin lesion formation by inhibiting inflammation and enhancing immunomodulation through the CD177/JAK2/STAT signaling pathway.
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