Li Yali, Wang Yuanyuan, Wu Yanping, Wang Baikui, Chen Xi, Xu Xin, Chen Hongliang, Li Weifen, Xu Xiaogang
Key Laboratory of Molecular Animal Nutrition and Feed Sciences, College of Animal Science, Zhejiang University, Hangzhou, 310058, PR China; Animal Nutrition and Human Health Laboratory, School of Life Sciences, Hunan Normal University, Changsha, 410006, PR China.
Key Laboratory of Molecular Animal Nutrition and Feed Sciences, College of Animal Science, Zhejiang University, Hangzhou, 310058, PR China.
Dev Comp Immunol. 2017 Aug;73:21-26. doi: 10.1016/j.dci.2017.03.002. Epub 2017 Mar 2.
Dendritic cells (DCs) comprise a system of highly professional antigen presenting cells (APCs) which connect innate and adaptive immunity by undergoing dramatic shift in their maturation state. Phytomedicine Echinacea purpurea extracts (EE) could modulate murine dendritic cell fate and function. However, the underlying mechanism of EE on DCs development and maturation remains limited. In this study, immature DCs were induced phenotypic maturation with up-regulated expression of key accessory molecules and the phagocytic activity was decreased after being treated with EE (400 μg/ml) for 48 h. We found that TLR1/2, JNK, p38-MAPK and NF-κB pathways were activated following EE exposure. Notably, JNK activation was demonstrated to be associated with increased IFN-γ response while p38-MAPK pathway exhibited immuno-regulatory effects via induction of IL-10 and TGF-β1. Furthermore, it was verified that NF-κB signaling was responsible for EE-induced synthesis of IFN-γ, IL-12 and TGF-β1, but not for IL-10 induction. These results indicate that EE have the immunomodulatory potency to promote both phenotypic and functional maturation of BMDCs via modulating the activation of JNK, p38-MAPK and NF-κB pathways. Our findings contributed to the current understanding of the immunoregulatory function of EE and the mechanism of DCs maturation.
树突状细胞(DCs)是由高度专业的抗原呈递细胞(APCs)组成的系统,通过在成熟状态下发生显著转变来连接先天性免疫和适应性免疫。植物药紫锥菊提取物(EE)可以调节小鼠树突状细胞的命运和功能。然而,EE对DCs发育和成熟的潜在机制仍不明确。在本研究中,未成熟的DCs经EE(400μg/ml)处理48小时后,诱导表型成熟,关键辅助分子的表达上调,吞噬活性降低。我们发现,EE处理后TLR1/2、JNK、p38-MAPK和NF-κB信号通路被激活。值得注意的是,JNK激活与IFN-γ反应增加有关,而p38-MAPK信号通路通过诱导IL-10和TGF-β1发挥免疫调节作用。此外,已证实NF-κB信号通路负责EE诱导的IFN-γ、IL-12和TGF-β1的合成,但不负责IL-10的诱导。这些结果表明,EE具有免疫调节能力,可通过调节JNK、p38-MAPK和NF-κB信号通路的激活来促进BMDCs的表型和功能成熟。我们的研究结果有助于当前对EE免疫调节功能和DCs成熟机制的理解。