School of Food Science and Engineering, Yangzhou University, Huayang Xilu 196, Yangzhou, Jiangsu 225127, People's Republic of China; School of Food and Biological Engineering, Jiangsu University, Xuefu Road 301, Zhenjiang, Jiangsu 212013, People's Republic of China.
School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Road 301, Zhenjiang, Jiangsu 212013, People's Republic of China.
Int J Biol Macromol. 2023 May 31;238:124108. doi: 10.1016/j.ijbiomac.2023.124108. Epub 2023 Mar 21.
Se-polysaccharide (Se-GFP-22) from Se-enriched Grifola frondosa has double and cooperative activities of polysaccharide and Se. To delineate the underlying mechanism and signaling cascade involved in immune-stimulatory property of Se-GFP-22, the production of cellular mediators and key proteins in signaling pathway was examined. Results showed that Se-GFP-22 exhibited no cytotoxic and had a high capacity to promote macrophage phagocytosis, up-regulate interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), and nitric oxide (NO) productions, as well as the relative messenger RNA (mRNA) expressions. In Se-GFP-22-induced macrophages, intracellular superoxide dismutase (SOD) activity was significantly increased to protect cells from oxidative injury. However, Se-GFP-22 induced macrophage activation was suppressed when the toll-like receptor 4 (TLR4) signaling pathway was blocked by a specific TLR4 inhibitor. According to the western blot analysis and the use of specific inhibitors against the mitogen-activated protein kinases (MAPK) signaling pathway, we speculated that Se-GFP-22 activated RAW264.7 macrophages through the TLR4-mediated MAPK signaling pathway. This study provides a molecular basis for the potential of Se-GFP-22 as a novel immune-stimulatory agent.
富硒金针菇来源的 Se-多糖（Se-GFP-22）具有多糖和硒的双重协同作用。为了阐明 Se-GFP-22 免疫刺激特性的潜在机制和信号级联，我们研究了细胞介质的产生和信号通路中的关键蛋白。结果表明，Se-GFP-22 无细胞毒性，具有促进巨噬细胞吞噬作用的高能力，上调白细胞介素 2（IL-2）、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和一氧化氮（NO）的产生以及相对信使 RNA（mRNA）的表达。在 Se-GFP-22 诱导的巨噬细胞中，细胞内超氧化物歧化酶（SOD）活性显著增加，以保护细胞免受氧化损伤。然而，当使用特定的 TLR4 抑制剂阻断 Toll 样受体 4（TLR4）信号通路时，Se-GFP-22 诱导的巨噬细胞激活被抑制。根据 Western blot 分析和使用针对丝裂原活化蛋白激酶（MAPK）信号通路的特异性抑制剂，我们推测 Se-GFP-22 通过 TLR4 介导的 MAPK 信号通路激活 RAW264.7 巨噬细胞。这项研究为 Se-GFP-22 作为一种新型免疫刺激剂的潜力提供了分子基础。
