Environmental Agents, Oxidative Stress and Autoimmunity

Abstract

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.

Keywords: Environmental agents; antioxidants; autoimmunity; oxidative stress; trichloroethylene.

Fig.1

Plausible mechanisms of oxidative stress (OS)-induced autoimmunity/autoimmune diseases (ADs). Environmental agents (EAs) induce excessive free radicals (ROS/RNS) that can potentially cause damage to molecules including lipids, proteins and DNA, resulting in lipid-derived reactive aldehydes (MAD/HNE) or ROS/RNS modified proteins and oxidative DNA damage. The modified proteins serve as neoantigens which can activate lymphocytes and reduce self-tolerance leading to autoimmunity. Oxidative DNA damage can lead to ADs by directly or indirectly (PARP-1 activation) inducing apoptosis. EA-mediated OS can also contribute to the development of ADs through activation of NLRP3 inflammasome, NF-κB, caspase-1, and IL-1β signaling pathways.