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Abstract：
Honey bee venom has been established to have significant effect in immunotherapy. In the present study, (Z)-11-eicosenol-a major constituent of bee venom, along with its derivations methyl cis-11-eicosenoate and cis-11-eicosenoic acid, were synthesised to investigate their immune stimulatory effect and possible use as vaccine adjuvants. Stimuli that prime and activate the immune system have exerted profound effects on immune cells, particularly macrophages; however, the effectiveness of bee venom constituents as immune stimulants has not yet been established. Here, the abilities of these compounds to act as pro-inflammatory stimuli were assessed, either alone or in combination with lipopolysaccharide (LPS), by examining the secretion of tumour necrosis factor-α (TNF-α) and the cytokines interleukin-1β (IL-1β), IL-6 and IL-10 by THP-1 macrophages. The compounds clearly increased the levels of IL-1β and decreased IL-10, whereas a decrease in IL-6 levels suggested a complex mechanism of action. A more in-depth profile of macrophage behaviour was therefore obtained by comprehensive untargeted metabolic profiling of the cells using liquid chromatography mass spectrometry (LC-MS) to confirm the ability of the eicosanoids to trigger the immune system. The level of 358 polar and 315 non-polar metabolites were changed significantly (p < 0.05) by all treatments. The LPS-stimulated production of most of the inflammatory metabolite biomarkers in glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, purine, pyrimidine and fatty acids metabolism were significantly enhanced by all three compounds, and particularly by methyl cis-11-eicosenoate and cis-11-eicosenoic acid. These findings support the proposed actions of (Z)-11-eicosenol, methyl cis-11-eicosenoate and cis-11-eicosenoic acid as immune system stimulators.
摘要：
蜂毒已被确定在免疫治疗中具有显著的效果。在本研究中,（Z）-11-二十烯醇-蜂毒的主要成分，及其衍生物顺式-11-二十碳烯酸甲酯和顺式-11-二十碳烯酸，被合成以研究它们的免疫刺激作用和可能用作疫苗佐剂。启动和激活免疫系统的刺激对免疫细胞产生了深远的影响，特别是巨噬细胞；然而，蜂毒成分作为免疫刺激剂的有效性尚未确定。这里,评估了这些化合物作为促炎刺激物的能力，单独或与脂多糖（LPS）联合使用，通过检测肿瘤坏死因子-α（TNF-α）和细胞因子白细胞介素-1β（IL-1β）的分泌，THP-1巨噬细胞的IL-6和IL-10。这些化合物明显增加了IL-1β的水平并降低了IL-10，而IL-6水平的降低表明了复杂的作用机制。因此，通过使用液相色谱质谱（LC-MS）对细胞进行全面的非靶向代谢分析来确认类花生酸触发免疫系统的能力，从而获得了巨噬细胞行为的更深入的概况。通过所有处理,358个极性代谢物和315个非极性代谢物的水平显著改变(p<0.05)。糖酵解中大多数炎症代谢物生物标志物的LPS刺激产生，三羧酸（TCA）循环，磷酸戊糖途径，嘌呤,嘧啶和脂肪酸代谢被所有三种化合物显著增强，特别是顺式-11-二十碳烯酸甲酯和顺式-11-二十碳烯酸。这些发现支持（Z）-11-二十烷醇的拟议行动，顺式-11-二十碳烯酸甲酯和顺式-11-二十碳烯酸作为免疫系统刺激剂。
