Department of Immunology, School of Preclinical Medicine, Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, People's Republic of China.
Department of Physiology, School of Preclinical Medicine, Guangxi Medical University, Nanning, People's Republic of China.
Immunopharmacol Immunotoxicol. 2020 Apr;42(2):119-127. doi: 10.1080/08923973.2020.1728310. Epub 2020 Feb 27.
Cordycepin has been shown to exhibit multiple pharmacological activities, such as antitumor, antifungi, antivirus, and immune-regulation activities, and is involved in the regulation of T cells. However, cordycepin that affects T cell activity is still not clear, and the molecular mechanism of cordycepin in regulation of TCR signaling has not yet been elucidated. In this study, the potential effect of cordycepin on T cells was observed in CFA-induced inflammation mice model, and the function of cordycepin in regulating TCR signaling cascade was investigated. A CFA-induced inflammation mice model was established for observing the effect of cordycepin on the thymus and spleen swellings, and T cell infiltration in paw tissue was detected by immunohistochemistry. The protein expression or phosphorilation was detected by western blotting, and the NFAT1 nuclear translocation was determined by fluorescence imaging. The cell proliferation, apoptosis, and IL-2 production were analyzed by CCK-8 method, flow cytometry, and ELISA. In the mice model, the thymus and spleen swellings were suppressed and the T cell infiltration in paw tissue was inhibited by cordycepin at a concentration of 10 mg/kg. Although the expressions of ZAP70 and PLCγ1 were not significantly changed in the human T cell line Jurkat with cordycepin pretreatment, the CD3-antibody-induced phosphorylations of ZAP70 and PLCγ1 were markedly blocked. The protein level of p85 decreased when Jurkat cells were pretreated with cordycepin, and cordycepin blocked TCR downstream molecule Erk phosphorylation and NFAT1 nuclear translocation. Further investigation revealed that cordycepin inhibited T cell proliferation, reduced IL-2 production, and induced T cell apoptosis. These findings suggest that cordycepin regulates TCR signaling to inhibit excessive T cell activation in inflammation. Thus, cordycepin may be a potential therapeutic application in inflammation-associated diseases.
蛹虫草素有多种药理活性，如抗肿瘤、抗真菌、抗病毒和免疫调节活性，并参与 T 细胞的调节。然而，影响 T 细胞活性的蛹虫草素仍不清楚，蛹虫草素调节 TCR 信号的分子机制尚未阐明。本研究在 CFA 诱导的炎症小鼠模型中观察蛹虫草素对 T 细胞的潜在影响，并研究蛹虫草素调节 TCR 信号级联的功能。建立 CFA 诱导的炎症小鼠模型，观察蛹虫草素对胸腺和脾脏肿胀以及 paw 组织中 T 细胞浸润的影响，采用免疫组织化学法检测 paw 组织中 T 细胞浸润。采用 Western blot 检测蛋白表达或磷酸化，荧光成像检测 NFAT1 核转位。采用 CCK-8 法、流式细胞术和 ELISA 分析细胞增殖、凋亡和 IL-2 产生。在该小鼠模型中，蛹虫草素以 10mg/kg 的浓度抑制胸腺和脾脏肿胀，并抑制 paw 组织中 T 细胞浸润。虽然蛹虫草素预处理人 T 细胞系 Jurkat 后 ZAP70 和 PLCγ1 的表达没有明显变化，但 CD3 抗体诱导的 ZAP70 和 PLCγ1 磷酸化明显被阻断。蛹虫草素预处理 Jurkat 细胞时，p85 蛋白水平降低，TCR 下游分子 Erk 磷酸化和 NFAT1 核转位被阻断。进一步研究表明，蛹虫草素抑制 T 细胞增殖，减少 IL-2 产生，诱导 T 细胞凋亡。这些发现表明，蛹虫草素通过调节 TCR 信号抑制炎症中过度的 T 细胞活化。因此，蛹虫草素可能在炎症相关疾病中具有潜在的治疗应用价值。
