School of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, 311121, China.
School of Life Sciences, China Jiliang University, Hangzhou, 310018, China.
Fish Shellfish Immunol. 2021 Jun;113:9-19. doi: 10.1016/j.fsi.2021.03.004. Epub 2021 Mar 14.
Perfluorooctanoic acid (PFOA) is widely used in industrial production due to its stable chemical structure and hydrophobic and oleophobic characteristics. PFOA has been frequently detected in environmental media and organisms, leading to increased health risks. There is a lack of information about the immunotoxicity of aquatic organisms induced by PFOA, and the molecular mechanisms remain unclear. In this study, LC-MS analysis proved that PFOA can accumulate in the kidney of zebrafish. In the 0.05 mg/L PFOA treatment group, the accumulation of PFOA in the kidney after 21 days of exposure significantly increased by 79.89%, compared to 14 days of exposure. And a hydropic endoplasmic reticulum, swelling of mitochondria and vacuolization were observed in kidney immune cells of zebrafish. The Toll-like receptor 2 (TLR2)/myeloid differentiation factor 88 (myd88)/NF-κB (P65) pathway was activated when PFOA exerted its effects, which led to regulation of antibody expression; RT-PCR results showed that the mRNA expression level of interleukin-4 (IL-4) decreased in a dose-dependent manner, decreasing to 29.6% of the control level in the 1 mg/L PFOA group after 21 d of exposure. According to triangle plot analysis, immunoglobulin exhibited a notable stress response to PFOA at an early phase; a high concentration of PFOA may disrupt the immune system of zebrafish. Third-order polynomial fitting analysis showed that the high-mRNA-expression regions of IL-4 and antibodies were partially consistent. The results indicated that PFOA could affect antibodies by increasing the concentrations of proinflammatory cytokines. Changes in antibody levels further influenced the expression of other cytokines, which eventually caused disorders in the zebrafish immune system. This study expands the understanding of PFOA-induced immunosuppression and suggests that toxicity mechanisms should be considered for further health risk assessment of emerging pollutants.
全氟辛酸（PFOA）由于其稳定的化学结构、疏水疏油性特点，被广泛应用于工业生产。PFOA 频繁出现在环境介质和生物体内，增加了健康风险。目前，关于 PFOA 对水生生物的免疫毒性及其分子机制的信息还比较缺乏。本研究通过 LC-MS 分析证实 PFOA 可在斑马鱼肾脏中蓄积。在 0.05 mg/L PFOA 处理组中，与 14 天暴露相比，21 天暴露后斑马鱼肾脏中 PFOA 的蓄积量显著增加了 79.89%。同时，斑马鱼肾脏免疫细胞中出现了水样内质网扩张、线粒体肿胀和空泡化。PFOA 作用后激活了 Toll 样受体 2（TLR2）/髓样分化因子 88（myd88）/核因子-κB（P65）通路，调节抗体表达；RT-PCR 结果表明，白细胞介素 4（IL-4）的 mRNA 表达水平呈剂量依赖性下降，在 1 mg/L PFOA 组暴露 21 天后下降至对照组的 29.6%。根据三角形图分析，在早期阶段，免疫球蛋白对 PFOA 表现出明显的应激反应；高浓度的 PFOA 可能破坏斑马鱼的免疫系统。三阶多项式拟合分析表明，IL-4 和抗体的高 mRNA 表达区域部分一致。结果表明，PFOA 可能通过增加促炎细胞因子的浓度来影响抗体。抗体水平的变化进一步影响其他细胞因子的表达，最终导致斑马鱼免疫系统紊乱。本研究扩展了对 PFOA 诱导免疫抑制的认识，并提示应考虑毒性机制，以进一步评估新兴污染物的健康风险。
