Selective effects of ginseng pectins on galectin-3-mediated T cell activation and apoptosis
Selective effects of ginseng pectins on galectin-3-mediated T cell activation and apoptosis
复制标题
人参果胶对半乳糖凝集素3介导的T细胞活化和凋亡的选择性作用
DOI：
10.1016/j.carbpol.2019.05.023
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发表时间：
2019
影响因子：
11.2
通讯作者：
Guihua Tai
中科院分区：
文献类型：
--
作者：
Huiting Xue;Zihan Zhao;Zhiying Lin;Jie Geng;Yuan Guan;Chengcheng Song;Yifa Zhou;Guihua Tai
半乳糖凝集素-3（Galectin-3，Gal-3）可诱导T细胞活化和凋亡，在肿瘤免疫耐受中发挥作用。在这里，我们证明了人参果胶选择性地抑制Gal-3诱导的T细胞凋亡，而不影响T细胞活化。这一发现与使用抑制两者的改性柑橘果胶（MCP）和马铃薯半乳聚糖（β-半乳聚糖）形成对比。尽管PKC/ERK和ROS/ERK途径参与T细胞活化和凋亡，但Ras/PI 3 K/Akt途径是T细胞活化所特有的。人参果胶选择性抑制ROS/ERK通路。使用其中Gal-3表达增加的Sarcomar-180小鼠模型，我们发现人参果胶（但不是MCP或β-半乳聚糖）显著促进T细胞增殖和IL-2表达，并抑制肿瘤生长45%。这些体内数据与果胶对Gal-3介导的T细胞凋亡和活化的选择性作用密切相关。我们的研究为开发靶向Gal-3功能的多糖类药物提供了一种新方法。
Galectin-3 (Gal-3) can induce T-cell activation and apoptosis and plays a role in tumor immune tolerance. Here, we demonstrate that ginseng pectins selectively inhibit Gal-3-induced T-cell apoptosis, while not affecting T-cell activation. This finding stands in contrast to that from the use of modified citrus pectin (MCP) and potato galactan (P-galactan) that inhibit both. Whereas PKC/ERK and ROS/ERK pathways are involved in both T-cell activation and apoptosis, the Ras/PI3K/Akt pathway is unique to T-cell activation. Ginseng pectins selectively inhibit the ROS/ERK pathway. Using the Sarcomar-180 mouse model in which Gal-3 expression is increased, we found that ginseng pectins (but not MCP or P-galactan) significantly promote T-cell proliferation and IL-2 expression, and inhibit tumor growth by 45%. These in vivo data correlate well with selective effects of pectins on Gal-3-mediated T-cell apoptosis and activation. Our study suggests a novel approach for the development of polysaccharide-based agents that target Gal-3 function.