Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia
Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia
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紫草素对重度再生障碍性贫血小鼠模型髓系树突状细胞功能的影响
DOI：
10.1155/2020/9025705
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发表时间：
2020-02
影响因子：
4.6
通讯作者：
Chunyan Liu
中科院分区：
文献类型：
--
作者：
Mengying Zheng;Bingnan Liu;Yuanyuan Shao;Luogang Hua;Rong Fu;Huaquan Wang;Ting Wang;Weiwei Qi;Zonghong Shao;Chunyan Liu
本研究旨在探讨丙酮酸激酶M2（PKM 2）抑制剂紫草素对全身照射联合淋巴细胞输注诱导的重型再生障碍性贫血（AA）小鼠模型骨髓树突状细胞（mDC）功能的影响。采用流式细胞术和qPCR检测AA小鼠PKM 2 + mDC的比例及其他免疫指标。葡萄糖消耗水平、丙酮酸生成水平和ATP含量用于确定mDC中的糖酵解代谢水平。用紫草素或免疫抑制剂环孢菌素A治疗AA小鼠，观察其存活率。AA小鼠表现为全血细胞减少，CD 4 +/CD 8+细胞比率降低，CD 8+细胞中穿孔素和颗粒酶水平升高，共刺激分子CD 80和CD 86表达增加，调节性T细胞数量不足。体内动物实验表明，紫草素介导的PKM 2表达的抑制与小鼠的高存活率相关。此外，环孢菌素A或紫草素的给药降低了CD 8+细胞上的细胞毒性分子和共刺激分子CD 80和CD 86的表达。综上所述，本研究的结果表明，紫草素可以抑制mDC的活化和增殖，以及下游的细胞毒性T细胞的活化，通过降低PKM 2在mDC中的水平。
This study is aimed at investigating the effects of shikonin, a pyruvate kinase M2 (PKM2) inhibitor, on the functions of myeloid dendritic cells (mDCs) in a mouse model of severe aplastic anemia (AA) generated by total body irradiation and lymphocyte infusion. Flow cytometry and qPCR were used to determine the proportions of PKM2+ mDCs and other immune indicators in the AA mice. Glucose consumption level, pyruvate generation level, and ATP content were used to determine the level of glycolytic metabolism in the mDCs. The survival rates of AA mice were evaluated after the administration of shikonin or the immunosuppressive agent cyclosporin A. The AA mice displayed pancytopenia, decreased CD4+/CD8+ cell ratio, increased perforin and granzyme levels in CD8+ cells, increased costimulatory CD80 and CD86 expressions, and inadequate regulatory T cell number. In vivo animal experiments showed that the shikonin-mediated inhibition of the PKM2 expression in mice was associated with high survival rates. In addition, the administration of cyclosporin A or shikonin decreased the expression of cytotoxic molecules and costimulatory CD80 and CD86 on CD8+ cells. Taken together, the results of this study indicated that shikonin could inhibit the activation and proliferation of mDCs as well as the activation of downstream cytotoxic T cells by reducing the PKM2 level in mDCs.
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紫草素通过抑制 C-MYC 和 PI3K/AKT/mTOR 通路在伯基特淋巴瘤中发挥抗肿瘤活性，并与阿霉素协同作用
影响因子：
4.6
作者：
Ni F;Huang X;Chen Z;Qian W;Tong X
通讯作者：
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影响因子：
4.6
作者：
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DOI：
10.1155/2013/379536
发表时间：
2013
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
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作者：
Li T;Yan F;Wang R;Zhou H;Liu L
通讯作者：
Liu L
DOI：
10.1084/jem.20031799
发表时间：
2004-04-05
期刊：
The Journal of experimental medicine
影响因子：
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作者：
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通讯作者：
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影响因子：
4.8
作者：
Morgan, Hugh P.;McNae, Iain W.;Walkinshaw, Malcolm D.
通讯作者：
Walkinshaw, Malcolm D.