Shikonin Suppresses Human T Lymphocyte Activation through Inhibition of IKK β Activity and JNK Phosphorylation.

Shikonin Suppresses Human T Lymphocyte Activation through Inhibition of IKK β Activity and JNK Phosphorylation.
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DOI:
10.1155/2013/379536
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发表时间:
2013
期刊:
Evidence-based complementary and alternative medicine : eCAM
影响因子:
--
通讯作者:
Liu L
Liu L
中科院分区:
其他
文献类型:
--
作者:
Li T;Yan F;Wang R;Zhou H;Liu L

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T 细胞在介导免疫反应以及人类炎症和自身免疫性疾病的发病机制中的关键作用已得到阐述。在目前的研究中,首先使用从血沉棕黄层分离的原代人 T 淋巴细胞检测了紫草素(一种从药用植物中分离出来的化合物)对 T 细胞活化的抑制作用。结果显示,紫草素剂量依赖性地抑制 T 细胞增殖、IL-2 和 IFN-γ 分泌、CD69 和 CD25 表达,以及 PMA/离子霉素或 OKT-3/CD28 单克隆抗体共刺激激活的细胞周期停滞。此外,发现紫草素介导的这些抑制反应与通过抑制 IKKα/β 磷酸化、IκB-α 磷酸化和降解以及通过直接降低 IKKβ 活性来抑制 NF-κB 核转位来抑制 NF-κB 信号通路有关。此外,紫草素还可抑制 T 细胞 MAPKs 通路中的 JNK 磷酸化。在这方面,我们得出结论,紫草素可以通过抑制 IKKβ 活性和 JNK 信号传导来抑制 T 淋巴细胞活化,这表明紫草素作为潜在的免疫抑制剂具有进一步研究的价值。
The key role of T cells has been elaborated in mediating immune responses and pathogenesis of human inflammatory and autoimmune conditions. In the current study the effect of shikonin, a compound isolated from a medicinal plant, on inhibition of T-cell activation was firstly examined by using primary human T lymphocytes isolated from buffy coat. Results showed that shikonin dose dependently suppressed T-cell proliferation, IL-2 and IFN-γ secretion, CD69 and CD25 expression, as well as cell cycle arrest activated by costimulation of PMA/ionomycin or OKT-3/CD28 monoclonal antibodies. Moreover, these inhibitory responses mediated by shikonin were found to be associated with suppression of the NF-κB signaling pathway via inhibition of the IKKα/β phosphorylation, IκB-α phosphorylation and degradation, and NF-κB nuclear translocation by directly decreasing IKKβ activity. Moreover, shikonin suppressed JNK phosphorylation in the MAPKs pathway of T cells. In this connection, we conclude that shikonin could suppress T lymphocyte activation through suppressing IKKβ activity and JNK signaling, which suggests that shikonin is valuable for further investigation as a potential immunosuppressive agent.
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