Abstract:
Significance: Reactive oxygen species (ROS), the reactive oxygen-carrying chemicals moieties, act as pleiotropic signal transducers to maintain various biological processes/functions, including immune response. Increased ROS production leads to oxidative stress, which is implicated in xenobiotic-induced adverse effects. Understanding the immunoregulatory mechanisms and immunotoxicity is of interest to developing therapeutics against xenobiotic insults. Recent Advances: While developmental studies have established the essential roles of ROS in the establishment and proper functioning of the immune system, toxicological studies have demonstrated high ROS generation as one of the potential mechanisms of immunotoxicity induced by environmental chemicals, including heavy metals, pesticides, aromatic hydrocarbons (benzene and derivatives), plastics, and nanoparticles. Mitochondrial electron transport and various signaling components, including NADH oxidase, toll-like receptors (TLRs), NF-κB, JNK, NRF2, p53, and STAT3, are involved in xenobiotic-induced ROS generation and immunotoxicity. Critical Issues: With many studies demonstrating the role of ROS and oxidative stress in xenobiotic-induced immunotoxicity, rigorous and orthogonal approaches are needed to achieve in-depth and precise understanding. The association of xenobiotic-induced immunotoxicity with disease susceptibility and progression needs more data acquisition. Furthermore, the general methodology needs to be possibly replaced with high-throughput precise techniques. Future Directions: The progression of xenobiotic-induced immunotoxicity into disease manifestation is not well documented. Immunotoxicological studies about the combination of xenobiotics, age-related sensitivity, and their involvement in human disease incidence and pathogenesis are warranted. Antioxid. Redox Signal. 40, 691-714.
摘要:
结论:活性氧(ROS),携带活性氧的化学物质,充当多效性信号换能器,以维持各种生物过程/功能,包括免疫反应。ROS产生增加导致氧化应激,这与外源性物质引起的不良反应有关。了解免疫调节机制和免疫毒性对于开发针对异种生物损伤的疗法很有意义。
背景:虽然发育研究已经确定了ROS在免疫系统的建立和正常运作中的重要作用,毒理学研究表明,高ROS产生是环境化学物质诱导的免疫毒性的潜在机制之一,包括重金属,杀虫剂,芳烃(苯和衍生物),塑料,和纳米粒子。线粒体电子传递和各种信号成分,包括NADH氧化酶,TLRs,NF-κB,JNK,NRF2、p53和STAT3参与外源性生物诱导的ROS产生和免疫毒性。
结果:许多研究表明ROS和氧化应激在外源性生物诱导的免疫毒性中的作用,需要严格和正交的方法来实现深入和准确的理解。外源性物质诱导的免疫毒性与疾病易感性和进展的关联需要更多的数据采集。此外,一般方法需要可能用高通量精确技术代替。
结论:异种生物诱导的免疫毒性向疾病表现的进展没有很好的记录。关于异种生物组合的免疫毒理学研究,与年龄相关的敏感性,它们参与人类疾病的发病率和发病机制是有必要的。