Wang Xin-Zhi, Nong Cheng, Jiang Zhen-Zhou, Zhang Lu-Yong
Jiangsu Key Laboratory of Drug Screening,China Pharmaceutical University Nanjing 210009,China Key Laboratory of Drug Quality Control and Pharmacovigilance,Ministry of Education,China Pharmaceutical University Nanjing 210009,China.
Jiangsu Key Laboratory of Drug Screening,China Pharmaceutical University Nanjing 210009,China.
Zhongguo Zhong Yao Za Zhi. 2019 Aug;44(15):3330-3334. doi: 10.19540/j.cnki.cjcmm.20181011.001.
Triptolide( TP) is isolated from the traditional Chinese medicine Tripterygium wilfordii,which exhibits notable immuneregulative effect. Th17 cells involve in inflammatory response and Treg cells contribute to immune tolerance. They both play an important role in immune response. Previous studies have investigated that TP induced hepatic Th17/Treg imbalance. However,the effect of TP on spleen Th17/Treg cells remains unclear. Therefore,the aim of present study was to investigate the effect of TP on Th17/Treg cells in spleen. In this study,the effect of TP on the proliferation of splenic lymphocyte was detected by cytotoxicity test in vitro. After different concentrations of TP( 2. 5,5,20,40 nmol·L(-1)) were given to splenic lymphocyte,cytokines secreted from the supernatant of splenic lymphocyte were detected by cytometric bead array,and the expression of suppressor of cytokine signaling( SOCS) mRNA was detected by qRT-PCR. Female C57 BL/6 mice were continuously observed for 24 h after treatment of 500 μg·kg-1 TP. The effects of TP on the splenic tissue structure and the percentage of Th17/Treg cells were examined. The results showed that the IC50 of TP was19. 6 nmol·L(-1) in spleen lymphocytes. TP inhibited the secretion of IL-2 and IL-10 and induced the expression of SOCS-1/3 mRNA in spleen lymphocytes at the dosage of 2. 5 and 5 nmol·L~(-1) after 24 h in vitro. Administration of TP at dosage of 500 μg·kg-1 had no significant spleen toxicity in vivo. TP treatment increased the percentage of Th17 cells after 12 h and inhibited the proportion of Treg cells after 12 and 24 h. In conclusion,TP reduced the secretion of IL-2 and IL-10 through SOCS-1/3 signaling pathway,thereby induced the percentage of Th17 cells and inhibited the percentage of Treg cells.
雷公藤甲素(TP)是从传统中药雷公藤中分离得到的,具有显著的免疫调节作用。Th17细胞参与炎症反应,而Treg细胞有助于免疫耐受。它们在免疫反应中都起着重要作用。以往研究发现TP可诱导肝脏Th17/Treg失衡。然而,TP对脾脏Th17/Treg细胞的影响仍不清楚。因此,本研究旨在探讨TP对脾脏Th17/Treg细胞的影响。在本研究中,通过体外细胞毒性试验检测TP对脾淋巴细胞增殖的影响。给脾淋巴细胞给予不同浓度的TP(2.5、5、20、40 nmol·L⁻¹)后,采用细胞计数珠阵列检测脾淋巴细胞上清液分泌的细胞因子,并用qRT-PCR检测细胞因子信号抑制因子(SOCS)mRNA的表达。雌性C57 BL/6小鼠在给予500 μg·kg⁻¹TP治疗后连续观察24 h。检测TP对脾脏组织结构及Th17/Treg细胞百分比的影响。结果显示,TP对脾淋巴细胞的半数抑制浓度(IC50)为19.6 nmol·L⁻¹。体外培养24 h后,2.5和5 nmol·L⁻¹剂量的TP可抑制脾淋巴细胞中IL-2和IL-10的分泌,并诱导SOCS-1/3 mRNA的表达。500 μg·kg⁻¹剂量的TP在体内对脾脏无明显毒性。TP处理12 h后可增加Th17细胞百分比,12和24 h后可抑制Treg细胞比例。综上所述,TP通过SOCS-1/3信号通路降低IL-2和IL-10的分泌,从而诱导Th17细胞百分比增加,抑制Treg细胞百分比。