Department of Biology, Norwegian University of Science and Technology, Trondheim, Norway.
Aquatic Ecology, University of Duisburg-Essen, Essen, Germany.
J Immunotoxicol. 2020 Dec;17(1):86-93. doi: 10.1080/1547691X.2020.1740838.
Many persistent organic pollutants, such as polychlorinated biphenyls (PCBs), have high immunomodulating potentials. Exposure to them, in combination with virus infections, has been shown to aggravate outcomes of the infection, leading to increased viral titers and host mortality. Expression of immune-related microRNA (miR) signaling pathways (by host and/or virus) have been shown to be important in determining these outcomes; there is some evidence to suggest pollutants can cause dysregulation of miRNAs. It was thus hypothesized here that modulation of miRNAs (and associated cytokine genes) by pollutants exerts negative effects during viral infections. To test this, an study on chicken embryo fibroblasts (CEF) exposed to a PCB mixture (Aroclor 1260) and then stimulated with a synthetic RNA virus (poly(I:C)) or infected with a lymphoma-causing DNA virus (Gallid Herpes Virus 2 [GaHV-2]) was conducted. Using quantitative real-time PCR, expression patterns for , pro-inflammatory α and , transcription factor κ, and anti-inflammatory were investigated 8, 12, and 18 h after virus activation. The study showed that Aroclor1260 modulated expression, such that a down-regulation of in poly(I:C)-treated CEF was seen up to 12 h. Aroclor1260 exposure also increased the mRNA expression of pro-inflammatory genes after 8 h in poly(I:C)-treated cells, but levels in GaHV-2-infected cells were unaffected. In contrast to with Aroclor1260/poly(I:C), Aroclor1260/GaHV-2-infected cells displayed an increase in levels after 12 h compared to levels seen with either individual treatment. While after 12 h expression of most evaluated genes was down-regulated (independent of treatment regimen), by 18 h, up-regulation was evident again. In conclusion, this study added evidence that signaling represents a sensitive pathway to chemically-induced immunomodulation and indicated that PCBs can modulate highly-regulated innate immune system signaling pathways important in determining host immune response outcomes during viral infections.
许多持久性有机污染物，如多氯联苯（PCBs），具有很高的免疫调节潜力。暴露于这些污染物，结合病毒感染，已被证明会加重感染的结果，导致病毒滴度增加和宿主死亡率增加。已经表明，宿主和/或病毒的免疫相关 microRNA（miR）信号通路的表达在决定这些结果方面很重要；有一些证据表明污染物会导致 miRNAs 失调。因此，这里假设污染物对 miRNAs（和相关细胞因子基因）的调节在病毒感染期间会产生负面影响。为了验证这一点，对鸡胚成纤维细胞（CEF）进行了一项研究，这些细胞暴露于多氯联苯混合物（Aroclor 1260）中，然后用合成 RNA 病毒（poly（I：C））或致淋巴瘤的 DNA 病毒（禽疱疹病毒 2 [GaHV-2]）刺激。使用定量实时 PCR，研究了病毒激活后 8、12 和 18 小时， 、促炎 α 和 、转录因子 κ 和抗炎 的表达模式。研究表明，Aroclor1260 调节了 的表达，以致于在 poly（I：C）处理的 CEF 中， 直到 12 小时都被下调。Aroclor1260 暴露还增加了 poly（I：C）处理细胞中 8 小时后促炎基因的 mRNA 表达，但 GaHV-2 感染细胞中的水平不受影响。与 Aroclor1260/poly（I：C）相比，Aroclor1260/GaHV-2 感染的细胞在 12 小时后与任何单个处理相比， 的水平升高。虽然在 12 小时后大多数评估基因的表达下调（独立于处理方案），但在 18 小时后，又出现了上调。总之，这项研究提供了证据表明，miR 信号代表了对化学诱导免疫调节敏感的途径，并表明 PCBs 可以调节在病毒感染期间决定宿主免疫反应结果的高度调控的先天免疫系统信号通路。
