Magaña-Guerrero Fátima Sofía, Domínguez-López Alfredo, Martínez-Aboytes Pamela, Buentello-Volante Beatriz, Garfias Yonathan
Biología Celular y Tisular, Unidad de Investigación, Instituto de Oftalmología Fundación Conde de Valenciana, Chimalpopoca 14, Ciudad de México, 06800, Mexico.
Departamento de Bioquímica, Facultad de Medicina, Universidad Nacional Autónoma de México, Av. Universidad 3000, Ciudad de México, 04510, Mexico.
Sci Rep. 2017 Sep 29;7(1):12426. doi: 10.1038/s41598-017-10962-2.
The mesenchymal stem cells obtained from human amniotic membrane (hAMSC) possess immunosuppressive functions through soluble factors such as prostanoids and proteins; thus, they have been proposed to ameliorate inflammatory processes. On the other hand, activated neutrophils are cells of the first line of immune defense that are able to release extracellular traps (NETs). NETs are formed of DNA and granular components; however, the excessive release of NETs is associated with the development of autoimmune and chronic inflammatory diseases. In this study, we identified that conditioned medium (CM) from hAMSC was able to diminish NETs release, as well as the production of reactive oxygen species (ROS) and the mitochondrial membrane potential from LPS-stimulated mouse bone marrow-derived neutrophils (BMN). Interestingly, NETs inhibition, ROS levels decrease and mitochondrial membrane potential loss were reverted when LPS-stimulated murine derived BMN were exposed to the CM from hAMSC transfected with TSG-6-siRNA. Finally, rhTSG6 was able to significantly diminish NETs release in BMN. These data suggest an inhibition mechanism of NETs ROS-dependent in which TSG-6 participates. Consequently, we propose the hAMSC use as a therapeutic candidate in the treatment of inflammatory diseases in which NETs are involved.
从人羊膜中获得的间充质干细胞（hAMSC）通过前列腺素和蛋白质等可溶性因子发挥免疫抑制功能；因此，它们被认为可改善炎症过程。另一方面，活化的中性粒细胞是免疫防御的第一线细胞，能够释放细胞外陷阱（NETs）。NETs由DNA和颗粒成分组成；然而，NETs的过度释放与自身免疫性疾病和慢性炎症性疾病的发展有关。在本研究中，我们发现hAMSC的条件培养基（CM）能够减少NETs的释放，以及脂多糖刺激的小鼠骨髓来源中性粒细胞（BMN）中活性氧（ROS）的产生和线粒体膜电位。有趣的是，当脂多糖刺激的小鼠来源BMN暴露于用TSG-6-siRNA转染的hAMSC的CM中时，NETs抑制、ROS水平降低和线粒体膜电位丧失得以恢复。最后，重组人TSG6能够显著减少BMN中NETs的释放。这些数据表明存在一种NETs的ROS依赖性抑制机制，其中TSG-6参与其中。因此，我们建议将hAMSC用作治疗涉及NETs的炎症性疾病的候选治疗方法。
