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Activation of Cholinergic Anti-Inflammatory Pathway in Peripheral Immune Cells Involved in Therapeutic Actions of α-Mangostin on Collagen-Induced Arthritis in Rats.

激活外周免疫细胞胆碱能抗炎通路参与 α-山竹素对大鼠胶原诱导性关节炎的治疗作用。

  • 影响因子:3.27
  • DOI:10.2147/DDDT.S249865
  • 作者列表:"Yin Q","Wu YJ","Pan S","Wang DD","Tao MQ","Pei WY","Zuo J
  • 发表时间:2020-05-22
Abstract

Background:Studies have shown that α-mangostin (MG) could exert anti-rheumatic effects in vivo by restoring immunity homeostasis, and have indicated that activation of the choline anti-inflammatory pathway (CAP) may contribute to this immunomodulatory property. The current study was designed to further investigate the effects of MG on the CAP in peripheral immune cells and clarify its relevance to the potential anti-rheumatic actions. Methods:The catalytic activity of acetylcholinesterase (AChE) and expression of α7-nicotinic cholinergic receptor (α7nAChR) in peripheral blood mononuclear cells (PBMCs) from rats with collagen-induced arthritis (CIA) or human volunteers were evaluated after MG treatment. Consequent influences on the immune environment were assessed by flow cytometry and ELISA analyses. Indirect effects on joints resulting from these immune changes were studied in a co-culture system comprised of fibroblast-like synoviocytes (FLSs) and PBMCs. Results:MG promoted α7nAChR expression in PBMCs both in vivo and in vitro, and inhibited the enzymatic activity of AChE simultaneously. Activation of the CAP was accompanied by a significant decrease in Th17 cells (CD4+IL-17A+), while no obvious changes concerning the distribution of other T-cell subsets were noticed upon MG treatment. Meanwhile, MG decreased the secretion of TNF-α and IL-1β under inflammatory conditions. PBMCs from MG-treated CIA rats lost the potential to stimulate NF-κB activation and pro-inflammatory cytokine production of FLSs in the co-culture system. Conclusion:Overall, the evidence suggested that MG can improve the peripheral immune milieu in CIA rats by suppressing Th17-cell differentiation through CAP activation, and achieve remission of inflammation mediated by FLSs.

摘要

背景: 研究表明 α-山竹素 (α-mangostin,MG) 在体内可通过恢复免疫稳态发挥抗风湿作用,并提示激活胆碱抗炎通路 (CAP) 可能有助于这种免疫调节特性。本研究旨在进一步研究 MG 在外周免疫细胞中对 CAP 的影响,并阐明其与潜在抗风湿作用的相关性。 方法: 观察胶原诱导性关节炎 (CIA) 大鼠外周血单个核细胞 (pbmc) 乙酰胆碱酯酶 (AChE) 的催化活性及 α 7-烟碱胆碱能受体 (α 7nachr) 的表达。或人类志愿者在 MG 治疗后进行评估。通过流式细胞术和 ELISA 分析评估对免疫环境的影响。在由成纤维样滑膜细胞 (FLSs) 和 PBMCs 组成的共培养系统中研究了这些免疫变化对关节的间接影响。 结果: MG 促进体内和体外 PBMCs 中 α 7nachr 的表达,同时抑制 AChE 的酶活性。CAP 的激活伴随着 Th17 细胞 (CD4 + IL-17A +) 的显著减少,而在 MG 治疗时,其他 t 细胞亚群的分布没有明显变化。同时,MG 降低炎症状态下 TNF-α 和 il-1 β 的分泌。Mgc 处理的 CIA 大鼠 pbmc 在共培养体系中失去了刺激 NF-κ b 活化和促炎细胞因子产生 FLSs 的潜力。 结论: 总体上,有证据表明,MG 可通过 CAP 激活抑制 Th17 细胞分化,改善 CIA 大鼠的外周免疫环境,达到缓解 FLSs 介导的炎症反应。

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