Background and purpose: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and joint destruction. Excessive proliferation of fibroblast-like synoviocytes (FLS) and over-expression of angiogenic factors play a crucial role in pannus formation and joint destruction in RA. Clarification of the role of cholinergic agonists in modulation of inflammation and immune system reactions is progressively ongoing. In this study, the anti-angiogenic effect of two cholinergic agonists, nicotine and ARR17779, on human FLS, and monocytic cell lines (U937) was evaluated.Experimental approach: The cells were cultured in DMEM supplemented with 10% FBS and treated with different doses of nicotine and ARR17779 in the presence of TNF-α, LPS, and IFN-γ. After 48 h, cell number was counted in different groups. After RNA extraction, cDNA was synthesized and the expression of VEGF and MMPs has been evaluated by real-time PCR using specific primers and probes. VEGF was assayed in U937 cell line supernatant using ELISA method.Key results: Both nicotine and ARR17779 inhibited FLS and U937 cell proliferation. Cholinergic agonists reduced the expression of MMPs and VEGF. VEGF level in supernatant of U937 cells treated with cholinergic agonists was also reduced.Conclusion and implications: Our results suggest that cholinergic agonists can modulate pathological conditions related to pannus formation in in-vitro conditions. Based on these results, cholinergic agonists can be considered as novel therapeutic options in RA. Further animal studies are needed before introducing these agents into clinical uses.

中文翻译：

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胆碱能激动剂抑制人成纤维样滑膜细胞和单核细胞系的增殖，并降低这些细胞的VEGF和MMPs表达。

背景与目的：类风湿关节炎（RA）是一种以炎症和关节破坏为特征的慢性自身免疫性疾病。成纤维细胞样滑膜细胞（FLS）的过度增殖和血管生成因子的过度表达在RA的pan形成和关节破坏中起关键作用。胆碱能激动剂在调节炎症和免疫系统反应中的作用的澄清正在逐步进行。本研究评估了两种胆碱能激动剂尼古丁和ARR17779对人FLS和单核细胞系（U937）的抗血管生成作用。实验方法：将细胞在添加了10％FBS的DMEM中培养，并用不同的方法处理。 TNF-α，LPS和IFN-γ存在时的最大剂量尼古丁和ARR17779。48小时后，对不同组的细胞数进行计数。RNA提取后 合成了cDNA，并使用特异性引物和探针通过实时PCR评估了VEGF和MMP的表达。ELISA法检测U937细胞系上清中的VEGF。主要结果：尼古丁和ARR17779均抑制FLS和U937细胞增殖。胆碱能激动剂降低了MMP和VEGF的表达。结论：胆碱能激动剂可以调节体外条件下与pan的形成相关的病理条件。基于这些结果，胆碱能激动剂可以被认为是RA的新型治疗选择。将这些药物引入临床之前，需要进行进一步的动物研究。