Arsenic exposure has become a matter of worldwide concern, which is associated with immune-related diseases. However, little is known about its effect on inflammatory immune-related homeostasis. The purpose of our study was to understand the potential tuning of above responses exerted by chronic arsenic exposure. Kunming mice were treated with 25 and 50 mg/L sodium arsenite for 1, 3 and 12 months via drinking water. At different endpoints of arsenic exposure, all animals and the whole spleen of the mice were weighed. The total arsenic levels of spleen were determined by the HPLC-HG-AFS method. Splenic NF-κB, MAPK and NRF2 protein levels by treatment of 25 mg/L NaAsO2 for 1, 3 and 12 months and 25 mg/L and 50 mg/L NaAsO2 for 12 months were assessed by western blot. Total RNA of spleen was isolated and relative mRNA levels of Foxp3, Il-10, Tnf-α, Il-6, Ifn-γ, Il-1β and Il-12 were measured by real-time PCR. Our results shown that NF-κB were continuously activated with treatment of 25 mg/L arsenic from 1, 3 to 12 months and 50 mg/L arsenic for 12 months. The transcription factor Foxp3 increased at 1 month but decreased at 3 and 12 months no matter 25 or 50 mg/L arsenic exposure. However, cytokine Il-10 always showed increased trend in mice treated with 25 or 50 mg/L arsenic for 1, 3 and 12 months. The transcriptional profiles of Tnf-α, Il-1β, Il-6, Ifn-γ and Il-12 revealed transient elevation at 1 and 3 months but shown significant decrease at 12 months on the whole. In addition, the sustained activation of inflammatory MAPK and anti-oxidative Nrf2 signaling pathways were observed in mice exposed to arsenic for 1, 3 and 12 months. In summary, our experiment in vivo suggested chronic arsenic exposure induces the time-dependent modulation of the inflammation and immunosuppression in spleen, which may be related to the activation of Tregs induced by MAPK/NF-κB as well as the increased transcription level of Foxp3 and Il-10.

中文翻译：

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慢性砷暴露诱导脾脏炎症和免疫抑制的时间依赖性调节。

砷暴露已成为全球关注的问题，这与免疫相关疾病有关。然而，关于它对炎症免疫相关稳态的影响知之甚少。我们研究的目的是了解慢性砷暴露对上述反应的潜在调整。昆明小鼠通过饮用水分别用 25 和 50 mg/L 亚砷酸钠处理 1、3 和 12 个月。在砷暴露的不同终点，称重所有动物和小鼠的整个脾脏。脾脏总砷含量采用 HPLC-HG-AFS 法测定。通过蛋白质印迹评估 25 mg/L NaAsO2 处理 1、3 和 12 个月以及 25 mg/L 和 50 mg/L NaAsO2 处理 12 个月后的脾脏 NF-κB、MAPK 和 NRF2 蛋白水平。分离脾脏的总 RNA 和 Foxp3、Il-10、Tnf-α、通过实时 PCR 测量 Il-6、Ifn-γ、Il-1β 和 Il-12。我们的研究结果表明，在 1、3 到 12 个月和 50 mg/L 砷处理 12 个月时，NF-κB 被持续激活。无论 25 或 50 mg/L 砷暴露量，转录因子 Foxp3 在 1 个月时增加，但在 3 个月和 12 个月时下降。然而，在用 25 或 50 mg/L 砷处理 1、3 和 12 个月的小鼠中，细胞因子 Il-10 总是显示出增加的趋势。Tnf-α、Il-1β、Il-6、Ifn-γ 和 Il-12 的转录谱显示在 1 个月和 3 个月时短暂升高，但在 12 个月时整体显示显着下降。此外，在暴露于砷 1、3 和 12 个月的小鼠中观察到炎症 MAPK 和抗氧化 Nrf2 信号通路的持续激活。总之，