Exposure to environmentally relevant doses of arsenic has several harmful effects on the human immune system. In traditional Eastern medicines, nettle has been used as an anti-inflammatory agent to treat rheumatism and osteoarthritis. Fumaric acid (FA) as a major effective compound in nettle was chosen based on very accurate virtual screening to find antagonist for TLR4/MD structure. In this study, the in vitro therapeutic effects of FA on arsenic-exposed monocytes-derived dendritic cells (MDDCs) were evaluated. All the canonical functions of dendritic cells in bridging innate and adaptive immune system including phagocytosis and antigen-presenting capacity, and also cytokines secretion, were evaluated after exposure to arsenic/FA. FA profoundly over-expressed antigen-presenting capacity of MDDCs after exposure to arsenic through the upregulation of MHCιι. However, phagocytosis capacity of arsenic-exposed MDDCs is not compensated for, by treatment with FA. Arsenic up-regulates pro-inflammatory cytokines independents of TLR4 pathway. FA surprisingly mitigates the up-regulation of IL-1β and TNF-α but not TLR4 and NF-kB. Moreover, FA increases the viability of MDDCs even at a high dose of arsenic. Totally, FA reduced inflammatory factors induced by arsenic. This finding confirmed that nettle and other medicinal plants containing similar structures with FA could be further analyzed as valuable candidates for the reduction of drastic effects of arsenic in human immune systems.

中文翻译：

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富马酸作为TLR-4途径的新型拮抗剂，可减轻人单核细胞衍生的树突状细胞中砷暴露的炎症。

暴露于与环境有关的剂量的砷对人体免疫系统有若干有害影响。在传统的东方药物中，荨麻已被用作治疗风湿病和骨关节炎的抗炎药。基于非常精确的虚拟筛选，选择了富马酸（FA）作为荨麻中的主要有效化合物，以发现TLR4 / MD结构的拮抗剂。在这项研究中，评估了FA对砷暴露于单核细胞的树突状细胞（MDDC）的体外治疗作用。接触砷/ FA后，评估树突状细胞在桥接先天和适应性免疫系统中的所有规范功能，包括吞噬作用和抗原呈递能力，以及细胞因子分泌。在通过上调MHC1而暴露于砷之后，FA深深地过度表达了MDDC的抗原呈递能力。但是，砷暴露的MDDC的吞噬能力不能通过用FA处理得到补偿。砷会上调TLR4途径的促炎细胞因子。FA令人惊讶地减轻了IL-1β和TNF-α的上调，但不减轻TLR4和NF-kB的上调。此外，即使在高剂量的砷下，FA也可提高MDDC的活力。总的来说，FA减少了砷诱导的炎症因子。这一发现证实，可以进一步分析含有与FA具有相似结构的荨麻和其他药用植物，作为减少砷对人体免疫系统的巨大影响的有价值的候选物。通过用FA治疗。砷会上调TLR4途径的促炎细胞因子。FA令人惊讶地减轻了IL-1β和TNF-α的上调，但不减轻TLR4和NF-kB的上调。此外，即使在高剂量的砷下，FA也可提高MDDC的活力。总的来说，FA减少了砷诱导的炎症因子。这一发现证实，含有FA相似结构的荨麻和其他药用植物可作为减少砷对人体免疫系统的猛烈影响的有价值的候选者，可作进一步分析。通过用FA治疗。砷上调TLR4途径的促炎细胞因子。FA令人惊讶地减轻了IL-1β和TNF-α的上调，但不减轻TLR4和NF-kB的上调。此外，即使在高剂量的砷下，FA也可提高MDDC的活力。总的来说，FA减少了砷诱导的炎症因子。这一发现证实，含有FA相似结构的荨麻和其他药用植物可作为减少砷对人体免疫系统的猛烈影响的有价值的候选者，可作进一步分析。