Department of Veterinary Medicine, College of Animal Sciences, Zhejiang University, Hangzhou 310058, PR China.
Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, Beijing 102206, PR China.
Int J Biol Macromol. 2020 Mar 15;147:616-628. doi: 10.1016/j.ijbiomac.2020.01.081. Epub 2020 Jan 10.
The present study was to elucidate the mechanisms underlying macrophage activation by total polysaccharides from Rhizoma Atractylodis Macrocephalae (RAMPtp). The results showed that RAMPtp significantly promoted productions of NO, ROS, cytokines and chemokines, enhanced pinocytic and phagocytic activity, and upregulated expressions of accessory and costimulatory molecules. RNA-seq analysis presented 2868 DEGs and 737 GO terms. PPI network analysis in combination with KEGG pathways as well as the western blot and functional verification assays indicated that NF-κB and STATs were the key regulators modulating the expressions of core gene TNF-α and IL-6 individually, and the transposition activation of NF-κB was identified as an early event in macrophage activation induced by RAMPtp. The involvements of MAPKs and PI3K-Akt pathways were also determined. These results indicated that immune response and immune function were regulated in RAMPtp-stimulated macrophages via a complex interaction network, in which NF-κB and Jak-STAT signaling pathways played a pivotal role.
本研究旨在阐明白术总多糖激活巨噬细胞的作用机制。结果表明，白术总多糖能显著促进 NO、ROS、细胞因子和趋化因子的产生，增强吞噬作用和吞噬能力，并上调辅助和共刺激分子的表达。RNA-seq 分析显示有 2868 个差异表达基因和 737 个 GO 术语。PPI 网络分析结合 KEGG 通路以及 Western blot 和功能验证实验表明，NF-κB 和 STATs 是单独调节核心基因 TNF-α和 IL-6 表达的关键调节剂，而 NF-κB 的转位激活被确定为 RAMPtp 诱导的巨噬细胞活化的早期事件。还确定了 MAPKs 和 PI3K-Akt 途径的参与。这些结果表明，免疫反应和免疫功能通过一个复杂的相互作用网络在 RAMPtp 刺激的巨噬细胞中得到调节，其中 NF-κB 和 Jak-STAT 信号通路发挥着关键作用。
