The focus of the present study was to examine the acute immunotoxic properties of oil sands process-affected waters (OSPW) using the RAW 264.7 macrophage cell line. Specifically, we used a quantitative PCR assay to monitor changes in the expression of stress, cytokine, and antimicrobial enzyme genes in activated macrophages following acute (i.e. < 24 h) exposure of the cells to whole OSPW and its fractions. Overall, our data shows that OSPW inorganic fraction (IF) significantly induces the expression of genes associated with oxidative stress and DNA damage and that the OSPW-IF also significantly augmented cytokine gene expression. These effects are similar to what was observed following whole OSPW exposures, which contrasts the minimal effects observed when cells were treated with equivalent doses of the OSPW organic fraction (OF). Surprisingly, OSPW-IF had reciprocal effects on gene and protein expression levels of two key macrophage enzymes (e.g. inducible nitric oxide (iNOS) synthase and arginase), which indicates that components within OSPW-IF have the unique ability to alter the overall functional states of macrophage by polarizing them towards an alternatively activated status; concomitant with the reciprocal depression of iNOS levels and enhanced expression and activity of arginase. Collectively, these findings show that at sub-lethal exposure doses, the inorganic constituents of OSPW have significant immunotoxicological properties that could potentially affect innate cellular defense responses of exposed animals.

中文翻译：

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受油砂加工影响的水中的无机成分诱导哺乳动物巨噬细胞应激基因的表达，并在基因和蛋白质水平上急性调节免疫细胞功能标记。

本研究的重点是使用RAW 264.7巨噬细胞系检查油砂工艺影响水（OSPW）的急性免疫毒性。具体来说，我们使用定量PCR分析法来监测细胞在急性（即<24小时）暴露于整个OSPW及其组分后在活化的巨噬细胞中压力，细胞因子和抗菌酶基因表达的变化。总的来说，我们的数据表明OSPW无机级分（IF）显着诱导了与氧化应激和DNA损伤相关的基因的表达，并且OSPW-IF也显着增强了细胞因子基因的表达。这些效应与整个OSPW暴露后所观察到的相似，这与当用等剂量的OSPW有机级分（OF）处理细胞时观察到的最小效应相反。出奇，OSPW-IF对两种关键的巨噬细胞酶（例如诱导型一氧化氮（iNOS）合酶和精氨酸酶）的基因和蛋白质表达水平具有相互影响，这表明OSPW-IF中的组分具有改变巨噬细胞总体功能状态的独特能力。使他们极化为交替激活状态；与iNOS水平的倒数降低以及精氨酸酶的表达和活性增强相关。总的来说，这些发现表明，在低于致死剂量的情况下，OSPW的无机成分具有显着的免疫毒理学特性，可能会潜在地影响暴露动物的先天细胞防御反应。这表明OSPW-IF内的组分具有独特的能力，可以通过使它们朝着交替激活的状态极化来改变巨噬细胞的整体功能状态；与iNOS水平的倒数降低以及精氨酸酶的表达和活性增强相关。总的来说，这些发现表明，在低于致死剂量的情况下，OSPW的无机成分具有显着的免疫毒理学特性，可能会潜在地影响暴露动物的先天细胞防御反应。这表明OSPW-IF内的组分具有独特的能力，可以通过使它们朝着交替激活的状态极化来改变巨噬细胞的整体功能状态；与iNOS水平的倒数降低以及精氨酸酶的表达和活性增强相关。总的来说，这些发现表明，在低于致死剂量的情况下，OSPW的无机成分具有显着的免疫毒理学特性，可能会潜在地影响暴露动物的先天细胞防御反应。