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