Glycyrrhizin regulates CD4+T cell response during liver fibrogenesis via JNK, ERK and PI3K/AKT pathway
Glycyrrhizin regulates CD4+T cell response during liver fibrogenesis via JNK, ERK and PI3K/AKT pathway
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甘草酸通过 JNK、ERK 和 PI3K/AKT 通路调节肝纤维化过程中 CD4 T 细胞反应
DOI：
10.1016/j.intimp.2012.08.013
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发表时间：
2012-12-01
影响因子：
5.6
通讯作者：
Jiang, Wei
中科院分区：
文献类型：
--
作者：
Tu, Chuan-tao;Li, Jing;Jiang, Wei
本研究的目的是阐明甘草甜素（GL）对肝纤维化过程中CD4（+）T细胞反应的免疫调节作用。为了获得关于 GL 对刀豆球蛋白 A (ConA) 诱导的小鼠模型肝脏和脾脏中 CD4(+)T 细胞影响的体内证据，给小鼠注射 ConA，同时给予或不给予 GL 8 周。接受 GL 治疗的小鼠可显着预防肝脏炎症和纤维化。此外，GL还抑制小鼠纤维化模型肝脏和脾脏中1型辅助性T细胞（Th）、Th2、Th17和调节性T细胞（Treg）的浸润，并分别调节肝脏中Th1/Th2和Treg/Th17平衡，使Th1和Treg谱系相对占优势。此外，GL 显着增强抗纤维化细胞因子干扰素 (IFN)-γ 和白细胞介素 (IL)-10。将浓度为10或100μg/mL的GL分别与ConA刺激的脾CD4(+)T细胞体外孵育，孵育过程中加入JNK抑制剂(SP600125)、ERK抑制剂(U0126)、p38抑制剂(SB203580)或PI3K/AKT抑制剂(LY29400225)。值得注意的是，GL不仅抑制ConA诱导的脾CD4(+)T细胞增殖，而且增强这些细胞中IFN-γ和IL-10的mRNA。与GL、SP600125、U0126和LY29400225的作用相似，但SB203580则不然，也抑制ConA诱导的CD4(+)T细胞增殖，表明JNK、ERK和PI3K/AKT参与了这一过程。此外，GL 在体外显着抑制 ConA 诱导的 JNK、ERK 和 PI3K/AKT 磷酸化。总的来说，GL 可能通过调节 JNK、ERK 和 PI3K/AKT 依赖性途径中的 CD4(+)T 细胞反应来减轻肝损伤和纤维化进展。 (c) 2012 Elsevier B.V. 保留所有权利。
The aims of this study were to elucidate the immunomodulatory effects of glycyrrhizin (GL) on CD4(+)T cell responses during liver fibrogenesis. To obtain in vivo evidence about the effects of GL on CD4(+)T cells in livers and spleens of concanavalin A (ConA)-induced mouse model, mice were administrated with ConA together with or without GL for 8 weeks. Mice treated with GL dramatically prevented liver inflammation and fibrosis. Besides, GL inhibited the infiltration of T helper (Th) cell type 1, Th2, Th17 and regulatory T cells (Treg) in livers and spleens of mouse fibrosis models, and regulated the Th1/Th2 and Treg/Th17 balances respectively to a relative dominance of Th1 and Treg lineages in livers. Moreover, GL dramatically enhanced the antifibrotic cytokine interferon (IFN)-gamma and interleukin (IL)-10. GL at a concentration of 10 or 100 mu g/mL was respectively incubated with ConA-stimulated splenic CD4(+)T cells in vitro, and JNK inhibitor (SP600125), ERK inhibitor (U0126), p38 inhibitor (SB203580) or PI3K/AKT inhibitor (LY29400225) was added during the incubation. Notably, GL not only inhibited ConA-induced proliferation of splenic CD4(+)T cells but also enhanced the mRNAs of IFN-gamma and IL-10 in these cells. Be similar to the effects of GL, SP600125, U0126 and LY29400225, however not SB203580, also inhibited ConA-induced CD4(+)T cell proliferation, indicating the involvement of JNK, ERK and PI3K/AKT in this process. Moreover, GL significantly inhibited ConA-induced phosphorylation of JNK, ERK and PI3K/AKT in vitro. Collectively, GL might alleviate liver injury and fibrosis progression via regulation of CD4(+)T cell response in JNK, ERK and PI3K/AKT-dependent pathways. (c) 2012 Elsevier B.V. All rights reserved.