1,4--d-葡聚糖甘露聚糖通过 TLR4 激活 NF-B 来调节免疫反应。
1,4--d-Glucomannan from Activates NF-B via TLR4 to Regulate the Immune Response.
机构信息
Key Laboratory of Pu-er Tea Science, Ministry of Education, Yunnan Agricultural University, Kunming 650201, China.
College of Science, Yunnan Agricultural University, Kunming 650201, China.
出版信息
Molecules. 2018 Oct 16;23(10):2658. doi: 10.3390/molecules23102658.
2,3--acetylated-1,4--d-glucomannan (DOP-1-1) is a polysaccharide isolated from the stem of . DOP-1-1 has been demonstrated to have remarkable immunomodulatory properties, but little is known about the influence of its structural diversity on bioactivity (and even less about the exact mechanism underlying its immune responses). First, DOP-1-1 was stabilized at different temperatures and pH conditions based on differential scanning calorimetry and size exclusion-chromatography⁻high-performance liquid chromatography. Then, a detailed study on the effects of DOP-1-1 on a human leukemia monocytic cell line (THP-1) under normal conditions was undertaken. DOP-1-1 promoted the translocation of nuclear factor-kappa B (NF-B) and degradation of IB proteins. The expression of genes and proteins closely associated with the immune, survival and apoptotic functions of NF-B were analyzed by quantitative real-time RT-PCR. Furthermore, CCL4 and IP10 were confirmed to be the novel targets of the immune response stimulated by DOP-1-1. The phosphorylation of NF-B was inhibited by treatment with a toll-like receptor 4 (TLR4) antagonist (TAK-242) and myeloid differentiation factor 88 (MyD88) inhibitor (ST2825). These data suggested: (i) the -acetylated glucomannan DOP-1-1 is present in the steady state in low-pH solutions; (ii) DOP-1-1 can induce an immune response through NF-B mediated by a TLR4 signaling pathway; and (iii) CCL4 and IP10 could be the novel targets of the immune response stimulated by -acetylated glucomannan.
2,3--乙酰化-1,4--d-葡聚糖（DOP-1-1）是从 中分离得到的多糖。DOP-1-1 已被证明具有显著的免疫调节特性，但关于其结构多样性对生物活性的影响知之甚少（甚至更少关于其免疫反应的确切机制）。首先，根据差示扫描量热法和尺寸排阻色谱-高效液相色谱，将 DOP-1-1 在不同温度和 pH 条件下进行稳定化。然后，在正常条件下对 DOP-1-1 对人白血病单核细胞系（THP-1）的影响进行了详细研究。DOP-1-1 促进核因子-kappa B（NF-B）的易位和 IB 蛋白的降解。通过定量实时 RT-PCR 分析与 NF-B 的免疫、存活和凋亡功能密切相关的基因和蛋白的表达。此外，CCL4 和 IP10 被确认为 DOP-1-1 刺激的免疫反应的新靶标。NF-B 的磷酸化通过用 Toll 样受体 4（TLR4）拮抗剂（TAK-242）和髓样分化因子 88（MyD88）抑制剂（ST2825）处理而被抑制。这些数据表明：（i）-乙酰化葡聚糖 DOP-1-1 在低 pH 溶液中处于稳定状态；（ii）DOP-1-1 可以通过 TLR4 信号通路介导的 NF-B 诱导免疫反应；和（iii）CCL4 和 IP10 可能是 -乙酰化葡聚糖刺激的免疫反应的新靶标。
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