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哇巴因影响人单核细胞激活标志物的表达、细胞因子的产生和内吞作用。

Ouabain affects the expression of activation markers, cytokine production, and endocytosis of human monocytes.

机构信息

Laboratório de Imunologia Tumoral, Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal do Rio de Janeiro, Centro de Ciências da Saúde, H 2 003 Cidade Universitária, Ilha do Fundão, 21941-590 Rio de Janeiro, Brazil.

出版信息

Mediators Inflamm. 2014;2014:760368. doi: 10.1155/2014/760368. Epub 2014 May 8.

DOI:10.1155/2014/760368
PMID:24904197
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4034513/
Abstract

Ouabain is a steroid capable of binding to and inhibiting Na(+),-K(+)-ATPase. Studies have demonstrated some actions of ouabain on immune cells, which indicated both pro- and anti-inflammatory properties of this molecule. Nevertheless, its effects on human monocytes are still poorly understood. Thus, the present work investigated effects of ouabain in the activation and function of human adherent monocytes. Our results show that there is an increase in intracellular calcium levels already 5 minutes following monocyte treatment with 10(-7) M of ouabain. Furthermore, monocytes expressed increased amounts of surface activation markers such as CD69, HLA-DR, CD86, and CD80 and also presented an augmented endocytic activity of dextran-FITC particles after 24 hours of culture in the presence of ouabain. However, monocytes treated with ouabain did not have an increased stimulatory capacity in allogeneic mixed leukocyte reaction. Ouabain-treated monocytes produced higher levels of IL-1 β and TNF- α as reported before. A novel observation was the fact that ouabain induced IL-10 and VEGF as well. Collectively, these results suggest that ouabain impacts monocyte activation and modulates monocyte functions, implying that this steroid could act as an immunomodulator of these cells.

摘要

哇巴因是一种能与 Na(+),-K(+)-ATP 酶结合并抑制其活性的甾体。研究表明哇巴因对免疫细胞具有一些作用,表明该分子具有促炎和抗炎特性。然而,其对人单核细胞的影响仍知之甚少。因此,本研究探讨了哇巴因对人贴壁单核细胞激活和功能的影响。我们的结果表明,在 10(-7) M 哇巴因处理单核细胞 5 分钟后,细胞内钙离子水平即升高。此外,在哇巴因存在的情况下培养 24 小时后,单核细胞表达了更多的表面激活标志物,如 CD69、HLA-DR、CD86 和 CD80,并且对葡聚糖-FITC 颗粒的内吞活性也增强。然而,在同种异体混合白细胞反应中,用哇巴因处理的单核细胞并没有增加刺激能力。如前所述,哇巴因处理的单核细胞产生更高水平的 IL-1β和 TNF-α。一个新的观察结果是,哇巴因诱导了 IL-10 和 VEGF 的产生。总之,这些结果表明哇巴因影响单核细胞的激活并调节单核细胞的功能,提示这种甾体可能作为这些细胞的免疫调节剂。

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本文引用的文献

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Cell signaling associated with Na(+)/K(+)-ATPase: activation of phosphatidylinositide 3-kinase IA/Akt by ouabain is independent of Src.与 Na(+)/K(+)-ATP 酶相关的细胞信号转导:哇巴因对磷酯酰肌醇 3-激酶 IA/Akt 的激活不依赖于 Src。
Biochemistry. 2013 Dec 17;52(50):9059-67. doi: 10.1021/bi4011804. Epub 2013 Nov 23.
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Ouabain activates NFκB through an NMDA signaling pathway in cultured cerebellar cells.哇巴因通过培养小脑细胞中的 NMDA 信号通路激活 NFκB。
Neuropharmacology. 2013 Oct;73:327-36. doi: 10.1016/j.neuropharm.2013.06.006. Epub 2013 Jun 15.
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Salt sensitivity, endogenous ouabain and hypertension.
Front Immunol. 2024 Jan 17;14:1287512. doi: 10.3389/fimmu.2023.1287512. eCollection 2023.
4
Neuroinflammation and Neutrophils: Modulation by Ouabain.神经炎症与中性粒细胞:哇巴因的调节作用
Front Pharmacol. 2022 Jan 31;13:824907. doi: 10.3389/fphar.2022.824907. eCollection 2022.
5
HIF1-Induced Glycolysis in Macrophage Is Essential for the Protective Effect of Ouabain during Endotoxemia.HIF1 诱导的巨噬细胞糖酵解对哇巴因在内毒素血症中的保护作用至关重要。
Oxid Med Cell Longev. 2019 Apr 28;2019:7136585. doi: 10.1155/2019/7136585. eCollection 2019.
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Ouabain Protects Mice Against Lipopolysaccharide-Induced Acute Lung Injury.哇巴因可保护小鼠免受脂多糖诱导的急性肺损伤。
Med Sci Monit. 2018 Jun 28;24:4455-4464. doi: 10.12659/MSM.908627.
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Much More than a Cardiotonic Steroid: Modulation of Inflammation by Ouabain.不仅仅是一种强心甾体:哇巴因对炎症的调节作用。
Front Physiol. 2017 Nov 10;8:895. doi: 10.3389/fphys.2017.00895. eCollection 2017.
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Ouabain attenuates ovalbumin-induced airway inflammation.哇巴因可减轻卵清蛋白诱导的气道炎症。
Inflamm Res. 2017 Dec;66(12):1117-1130. doi: 10.1007/s00011-017-1092-9. Epub 2017 Sep 13.
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On the Many Actions of Ouabain: Pro-Cystogenic Effects in Autosomal Dominant Polycystic Kidney Disease.哇巴因的多种作用:对常染色体显性多囊肾病的促囊肿形成作用
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