Faculty of Agriculture, Department of Plant Breeding and Biotechnology, University of Zabol , Zabol , Iran.
Research Institute of Modern Biological Techniques, University of Zanjan , Zanjan , Iran.
Immunopharmacol Immunotoxicol. 2019 Aug;41(4):513-520. doi: 10.1080/08923973.2019.1645166. Epub 2019 Aug 9.
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 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.
砷暴露在环境相关剂量下对人体免疫系统有多种有害影响。在传统的东方医学中，荨麻已被用作抗炎剂来治疗风湿和骨关节炎。基于非常准确的虚拟筛选，选择了荨麻中的主要有效化合物富马酸（FA），以寻找 TLR4/MD 结构的拮抗剂。在这项研究中，评估了 FA 对砷暴露的单核细胞衍生的树突状细胞（MDDC）的治疗作用。在暴露于砷/FA 后，评估了树突状细胞在桥接先天和适应性免疫系统方面的所有典型功能，包括吞噬作用和抗原呈递能力，以及细胞因子分泌。FA 通过上调 MHCιι，显著增强了砷暴露的 MDDC 的抗原呈递能力。然而，FA 治疗并不能补偿砷暴露的 MDDC 的吞噬能力。砷独立于 TLR4 途径上调促炎细胞因子。FA 出人意料地减轻了 IL-1β和 TNF-α的上调，但没有减轻 TLR4 和 NF-kB。此外，FA 甚至在高剂量砷的情况下增加了 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，荨麻和其他含有与 FA 相似结构的药用植物可以进一步分析为减少砷对人体免疫系统的剧烈影响的有价值的候选物。
