Khan M Firoze, Wang Gangduo
Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555.
Curr Opin Toxicol. 2018 Feb;7:22-27. doi: 10.1016/j.cotox.2017.10.012. Epub 2017 Oct 26.
Oxidative stress (OS) plays an important role in the pathogenesis of a variety of autoimmune diseases (ADs) and many environmental agents participate in this process. Environmental agents, including trichloroethylene (TCE), silica, pristane, mercury, and smoke, are known to induce an autoimmune response, potentially through OS-mediated mechanisms. Here, we focus on unraveling the targets and signaling pathways that have been mechanistically linked with OS, as a result of exposure to these and numerous other environmental agents, and their impact on the immune system in triggering ADs. Antioxidants and molecular targets impeding autoimmunity by targeting specific signaling pathways are also reviewed. The review not only provides an overview of the current knowledge and evidence showing strong associations between environmental exposures, OS, and ADs, but also plausible mechanisms by which OS causes autoimmunity/ADs. We also discuss areas that require additional approaches, such as unraveling specific events/mechanisms leading to such devastating diseases and measures to prevent or attenuate such diseases.
氧化应激（OS）在多种自身免疫性疾病（ADs）的发病机制中起重要作用，许多环境因素参与了这一过程。已知包括三氯乙烯（TCE）、二氧化硅、 pristane、汞和烟雾在内的环境因素可诱导自身免疫反应，可能是通过OS介导的机制。在这里，我们专注于揭示由于接触这些以及许多其他环境因素而与OS在机制上相关联的靶点和信号通路，以及它们对触发ADs的免疫系统的影响。还综述了通过靶向特定信号通路来阻止自身免疫的抗氧化剂和分子靶点。该综述不仅概述了当前显示环境暴露、OS和ADs之间存在强关联的知识和证据，还阐述了OS导致自身免疫/ADs的合理机制。我们还讨论了需要额外研究方法的领域，例如揭示导致此类毁灭性疾病的具体事件/机制以及预防或减轻此类疾病的措施。
