Glycyrrhizin alleviates Con A-induced hepatitis by differentially regulating the production of IL-17 and IL-25
Glycyrrhizin alleviates Con A-induced hepatitis by differentially regulating the production of IL-17 and IL-25
复制标题
甘草甜素通过差异调节 IL-17 和 IL-25 的产生来缓解 Con A 诱导的肝炎
DOI：
10.1016/j.biopha.2018.12.025
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发表时间：
2018
影响因子：
7.5
通讯作者：
Min Fang
中科院分区：
文献类型：
--
作者：
Yuanyue Zhang;Lingyun Li;Chang Qi;Shuyao Hua;Xiaoyuan Fei;Feili Gong;Min Fang
甘草甜素是一种三萜类化合物，已被报道为一种抗炎药，用于治疗包括肝炎在内的各种炎症性疾病。然而，甘草酸抑制炎症的机制尚不清楚。在Con A诱导的小鼠肝炎模型上，我们发现给予甘草酸苷可以减轻ConA诱导的肝损伤，表现为炎症细胞因子干扰素-γ、IL-6和IL-17的产生减少，以及血清丙氨酸转氨酶(ALT)的减少。阻断IL-17可显著减轻Con A挑战引起的肝损伤。有趣的是，与单独注射ConA相比，注射甘草酸苷和ConA的小鼠，无论是在mRNA水平还是在蛋白水平上，内源性Alarmin炎症分子高迁移率族蛋白1(HMGB1)都显著降低。相反，在ConA挑战的情况下给予甘草酸苷可上调IL-25的产生。此外，IL-25升高可诱导保护性淋巴细胞亚群Gr-1+CD11b+(髓源性抑制细胞，MDSCs)比例增加，从而抑制免疫细胞的活化，有利于ConA刺激引起的不良免疫反应的解决。结果表明，甘草酸对Con A诱导的小鼠肝炎有保护作用。这种保护作用尤其与减少IL-17的产生和增强IL-25的表达有关。本研究可能为临床治疗急性肝炎提供一种新的策略。
Glycyrrhizin, a triterpenoid compound, has been reported to be an anti-inflammatory agent for the treatment of a variety of inflammatory diseases including hepatitis. However, the mechanism by which glycyrrhizin inhibits inflammation is unclear. Using a Con A-induced hepatitis model in mice, we found that administration of glycyrrhizin ameliorates Con A-induced liver injury, which manifests as reduction in the production of inflammatory cytokines IFN-γ, IL-6 and IL-17, as well as serum alanine aminotransferase (ALT). Blockade of IL-17 dramatically mitigates liver injury resulting from Con A challenge. Interestingly, at both the mRNA and protein levels, the endogenous alarmin inflammatory molecule high-mobility group box 1 (HMGB1) is significantly decreased in mice injected with glycyrrhizin combined with Con A compared to those injected with Con A alone. In contrast, the administration of glycyrrhizin with Con A challenge up-regulates the production of IL-25. Furthermore, an increase in the proportion of protective lymphocyte subset, Gr-1+CD11b+(Myeloid-Derived Suppressor Cell, MDSCs), could be induced by increased IL-25 to restrain immune cell activation and favor the resolution of detrimental immune reactions caused by Con A challenge. The results indicate that glycyrrhizin plays a protective role in Con A-induced hepatitis. This protective role is particularly associated with reducing the production of IL-17 and enhancing the expression of IL-25. The present study may provide a new strategy for the treatment of acute hepatitis in the clinical setting.