Huang Yin-Qiu, Li Peng-Yan, Wang Jia-Bo, Zhou Hou-Qin, Yang Zhi-Rui, Yang Rui-Chuang, Bai Zhao-Fang, Wang Li-Fu, Li Jian-Yu, Liu Hong-Hong, Zhao Yan-Ling, Xiao Xiao-He
Pharmacy College, Chengdu University of Traditional Chinese MedicineChengdu, China; Department of Pharmacy, 302 Military Hospital of ChinaBeijing, China.
China Military Institute of Chinese Medicine, 302 Military Hospital of China Beijing, China.
Front Pharmacol. 2016 Aug 12;7:256. doi: 10.3389/fphar.2016.00256. eCollection 2016.
Increasing evidence has suggested that natural killer (NK) cells contribute to the pathogenesis of human immunological liver injury (ILI). Previous studies have demonstrated that Sophocarpine exerts activity in immune modulation. It also has a therapeutic effect on liver protection in that it can alleviate liver fibrosis by suppressing both the activation of hepatic stellate cells and the proliferation of the activated hepatic stellate cells. However, whether Sophocarpine protects the liver by regulating NK cell activity remains unclear. In this study, the modulating effect of Sophocarpine on NK cells in the liver was investigated. The results showed that Sophocarpine dramatically decreased the production of pro-inflammatory cytokines and attenuated the liver injury induced by Poly I: C/D-GalN in C57BL/6- mice. More importantly, Sophocarpine pre-treatment significantly suppressed NK cell activation and downregulated the expression of NKG2D, a receptor responsible for NK cell activation. Moreover, the protein levels of DAP12, ZAP76 and Syk decreased, as did their corresponding mRNA levels. Overall, our study demonstrates that Sophocarpine inhibits NK cell activity, thus making it a promising therapy for ILI.
越来越多的证据表明,自然杀伤(NK)细胞参与人类免疫性肝损伤(ILI)的发病机制。先前的研究表明,槐果碱具有免疫调节活性。它对肝脏保护也有治疗作用,因为它可以通过抑制肝星状细胞的激活和活化肝星状细胞的增殖来减轻肝纤维化。然而,槐果碱是否通过调节NK细胞活性来保护肝脏仍不清楚。在本研究中,研究了槐果碱对肝脏中NK细胞的调节作用。结果表明,槐果碱显著降低促炎细胞因子的产生,并减轻了Poly I:C/D-GalN诱导的C57BL/6小鼠肝损伤。更重要的是,槐果碱预处理显著抑制NK细胞活化,并下调负责NK细胞活化的受体NKG2D的表达。此外,DAP12、ZAP76和Syk的蛋白水平及其相应的mRNA水平均降低。总体而言,我们的研究表明槐果碱抑制NK细胞活性,因此使其成为ILI的一种有前景的治疗方法。