Autoimmune potential of perchloroethylene: Role of lipid-derived aldehydes.
Autoimmune potential of perchloroethylene: Role of lipid-derived aldehydes.
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DOI：
10.1016/j.taap.2017.08.009
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发表时间：
2017-10-15
影响因子：
3.8
通讯作者：
Khan MF
中科院分区：
文献类型：
--
作者：
Wang G;Wang J;Ansari GAS;Khan MF
四氯乙烯（PCE）是一种普遍存在的环境污染物，可诱发自身免疫性疾病，包括系统性红斑狼疮（SLE）和硬皮病。然而，实验证据表明PCE在介导自身免疫中的潜力是缺乏的。因此，本研究旨在探索PCE诱导/加重自身免疫反应的潜力。将6周龄雌性MRL+/+小鼠（每组6只）通过饮用水用PCE（0.5 mg/ml）处理12、18和24周，并评价自身免疫和氧化应激的标志物。PCE暴露导致血清抗核抗体（ANA），抗dsDNA和抗硬皮病-70（抗Scl-70）抗体在18周时显著增加，在24周时更大程度上增加，表明PCE暴露加剧了我们动物模型中的自身免疫。自身抗体的增加与丙二醛（MDA）-蛋白加合物及其抗体的时间依赖性增加，以及抗氧化剂GSH和SOD的水平显着降低。从用PCE处理18周和24周的小鼠中分离的脾细胞显示出更大的Th 17细胞增殖，并且在用MDA-小鼠血清白蛋白加合物刺激后培养上清液中IL-17的释放增加，这表明MDA修饰的蛋白质可以通过激活Th 17细胞来充当免疫触发剂，并且有助于PCE介导的自身免疫。因此，我们的研究提供了一个实验证据，PCE诱导/加剧自身免疫反应和脂质衍生的醛（如MDA）有助于这种反应。
Tetrachloroethene (perchloroethylene, PCE), an ubiquitous environmental contaminant, has been implicated in inducing autoimmunity/autoimmune diseases (ADs), including systemic lupus erythematosus (SLE) and scleroderma in humans. However, experimental evidence suggesting the potential of PCE in mediating autoimmunity is lacking. This study was, therefore, undertaken to explore PCE’s potential in inducing/exacerbating an autoimmune response. Six-week old female MRL+/+ mice, in groups of 6 each, were treated with PCE (0.5 mg/ml) via drinking water for 12, 18 and 24 weeks and markers of autoimmunity and oxidative stress were evaluated. PCE exposure led to significant increases in serum anti-nuclear antibodies (ANA), anti-dsDNA and anti-scleroderma-70 (anti-Scl-70) antibodies at 18 weeks and, to a greater extent at 24 weeks, suggesting that PCE exposure exacerbated autoimmunity in our animal model. The increases in autoantibodies were associated with time-dependent increases in malondialdehyde (MDA)-protein adducts and their antibodies, as well as significantly decreased levels of antioxidants GSH and SOD. The splenocytes isolated from mice treated with PCE for 18 and 24 weeks showed greater Th17 cell proliferation and increased release of IL-17 in culture supernatants following stimulation with MDA-mouse serum albumin adducts, suggesting that MDA-modified proteins may act as an immunologic trigger by activating Th17 cells and contribute to PCE-mediated autoimmunity. Our studies thus provide an experimental evidence that PCE induces/exacerbates an autoimmune response and lipid-derived aldehydes (such as MDA) contribute to this response.
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