Department of Occupational Health and Environment Health, School of Public Health, Anhui Medical University, Hefei, Anhui, China.
Institute of Dermatology, the First Affiliated Hospital, Anhui Medical University, Hefei, Anhui 230022, China.
Ecotoxicol Environ Saf. 2019 May 15;172:105-113. doi: 10.1016/j.ecoenv.2019.01.049. Epub 2019 Jan 24.
Trichloroethylene (TCE) is a major occupational and environmental chemical compound which causes occupational dermatitis medicamentosa-like of TCE with severe liver damage. Our previous studies showed that complement activation was a newly recognized mechanism for TCE-induced liver damage. The objective of this study was to explore the role of the key complement regulatory protein, CD59a, in TCE-induced immune liver injury. We firstly evaluated the changes of CD59a expression in liver tissue and then investigated if the changes were associated with membrane attack complex (MAC) formation, nuclear factor kappa B (NF-κB) activation and liver damage in BALB/c mice model of TCE-induced skin sensitization in the absence or presence of soluble recombinant rat CD59-Cys. The results showed that low expression of CD59a accompanied by MAC deposition in the liver of TCE-sensitized BALB/c mice, which was consistent in time. In addition, activation of NF-κB pathway, upregulation of inflammatory cytokine and liver damage also occured. Additional experiment showed that recombinant rat sCD59-Cys alleviated inflammation and liver damage in TCE-sensitized BALB/c mice. Moreover, recombinant rat sCD59-Cys reduced MAC formation and inhibited NF-κB activation measured by P-IκBα and nuclear NF-κB p65 in the liver of TCE-sensitized BALB/c mice. In conclusion, recombinant rat sCD59-Cys plays a protective role in immune liver injury of TCE-sensitized BALB/c mice.
三氯乙烯(TCE)是一种主要的职业和环境化学化合物,可引起 TCE 所致职业性药疹样皮炎伴严重肝损伤。我们之前的研究表明,补体激活是 TCE 诱导肝损伤的一种新的公认机制。本研究旨在探讨关键补体调节蛋白 CD59a 在 TCE 诱导的免疫性肝损伤中的作用。我们首先评估了肝组织中 CD59a 表达的变化,然后研究了这种变化是否与膜攻击复合物(MAC)形成、核因子 kappa B(NF-κB)激活以及 TCE 诱导的 BALB/c 小鼠皮肤致敏模型中的肝损伤有关,在该模型中存在或不存在可溶性重组大鼠 CD59-Cys。结果表明,TCE 致敏的 BALB/c 小鼠肝组织中 CD59a 低表达,同时伴有 MAC 沉积,这种变化具有时间一致性。此外,NF-κB 通路的激活、炎症细胞因子的上调和肝损伤也发生了。额外的实验表明,重组大鼠 sCD59-Cys 减轻了 TCE 致敏的 BALB/c 小鼠的炎症和肝损伤。此外,重组大鼠 sCD59-Cys 减少了 TCE 致敏的 BALB/c 小鼠肝组织中 MAC 形成,并抑制了 P-IκBα 和核 NF-κB p65 测量的 NF-κB 激活。总之,重组大鼠 sCD59-Cys 在 TCE 致敏的 BALB/c 小鼠免疫性肝损伤中发挥保护作用。