Department of Medicine 3, Friedrich Alexander University of Erlangen-Nürnberg, Universitätsklinikum Erlangen, Germany.
Health and Medical Sciences, University of Surrey, Guildford, UK.
Free Radic Biol Med. 2018 Sep;125:62-71. doi: 10.1016/j.freeradbiomed.2018.03.016. Epub 2018 Mar 15.
Reactive oxygen species (ROS) are created in cells during oxidative phosphorylation by the respiratory chain in the mitochondria or by the family of NADPH oxidase (NOX) complexes. The first discovered and most studied of these complexes, NOX2, mediates the oxidative burst in phagocytes. ROS generated by NOX2 are dreadful weapons: while being essential to kill ingested pathogens they can also cause degenerative changes on tissue if production and release are not balanced by sufficient detoxification. In the last fifteen years evidence has been accumulating that ROS are also integral signaling molecules and are important for regulating autoimmunity and immune-mediated inflammatory diseases. It seems that an accurate redox balance is necessary to sustain an immune state that both prevents the development of overt autoimmunity (the bright side of ROS) and minimizes collateral tissue damage (the dark side of ROS). Herein, we review studies from rodent models of arthritis, lupus, and neurodegenerative diseases that show that low NOX2-derived ROS production is linked to disease and elaborate on the underlying cellular and molecular mechanisms and the translation of these results to disease in humans.
活性氧 (ROS) 在细胞内是由线粒体呼吸链或 NADPH 氧化酶 (NOX) 复合物家族在氧化磷酸化过程中产生的。这些复合物中最早发现和研究最多的是 NOX2，它介导吞噬细胞中的氧化爆发。NOX2 产生的 ROS 是可怕的武器：虽然它们对于杀死摄入的病原体是必不可少的，但如果产生和释放不能通过足够的解毒来平衡，它们也会导致组织的退行性变化。在过去的十五年中，有证据表明 ROS 也是完整的信号分子，对于调节自身免疫和免疫介导的炎症性疾病很重要。似乎需要一个准确的氧化还原平衡来维持一种免疫状态，这种状态既能防止明显自身免疫的发展（ROS 的光明面），又能将组织损伤的附带损害降到最低（ROS 的黑暗面）。本文综述了关节炎、狼疮和神经退行性疾病的啮齿动物模型研究，这些研究表明，NOX2 衍生的 ROS 产生减少与疾病有关，并详细阐述了潜在的细胞和分子机制，以及这些结果在人类疾病中的转化。
