Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Science, Shantou University, Shantou, Guangdong, 515063, China.
Guangdong Provincial Key Laboratory of Marine Biotechnology, Institute of Marine Science, Shantou University, Shantou, Guangdong, 515063, China; Faculty of Veterinary and Animal Science, Department of Biotechnology, Lasbela Univesity of Agriculture Water and Marine Science, 89250, Uthal, Balochistan, Pakistan.
Chemosphere. 2020 Sep;254:126717. doi: 10.1016/j.chemosphere.2020.126717. Epub 2020 Apr 10.
Pantropical spotted dolphins are apex predators and have a long lifespan, which makes them susceptible to chemical pollutants such as polybrominated diphenyl ethers (PBDEs), which are associated with immunotoxicity in wildlife. However, the effects of PBDEs and their mechanism of immunotoxicity in dolphins is largely unknown. Previously, we established fibroblast cell lines obtained from pantropical spotted dolphins (PSD-LWHT) as an in vitro model for assessing the toxicological implications of chemical pollutants in dolphins. In this study, we used the novel immortalized fibroblast cell line to explore the potential immune stimulation effect of PBDEs via prostaglandins signaling pathways to better understand the immunotoxicity pathway of PBDEs in dolphins. BDE-47, -100, and -209 exposure generally resulted in an increase in inflammatory cytokine expression, PGE levels, and COX-2 gene expression but BDE-209 resulted in a suppression in IL-10 production. Both protein and mRNA expression of COX-2 and PTGES increased significantly following exposure to the PBDEs. The results suggested BDE-100 and -209 increased prostaglandin E (PGE) production via increased expression of COX-2 and PTGES expression. Only BDE-100 increased expression level of the prostaglandin E receptor EP4 while BDE-47 and BDE-209 decreased its expression. This probably explained why suppressive effect on the expression level of anti-inflammatory cytokines were only found in exposure with BDE-47 and BDE-209 rather than BDE-100. The results showed that PBDEs stimulate innate immune response by triggering PGE-EPs-cAMP-cytokines signaling.
热带斑海豚是顶级掠食者，寿命较长，因此易受到多溴联苯醚（PBDEs）等化学污染物的影响，这些污染物与野生动物的免疫毒性有关。然而，PBDEs 及其在海豚中的免疫毒性机制在很大程度上尚不清楚。此前，我们建立了来自热带斑海豚（PSD-LWHT）的成纤维细胞系，作为评估海豚中化学污染物毒理学影响的体外模型。在这项研究中，我们使用新型永生化成纤维细胞系通过前列腺素信号通路探索 PBDEs 的潜在免疫刺激作用，以更好地了解 PBDEs 在海豚中的免疫毒性途径。BDE-47、-100 和-209 暴露通常会导致炎症细胞因子表达、PGE 水平和 COX-2 基因表达增加，但 BDE-209 会抑制 IL-10 产生。暴露于 PBDE 后，COX-2 和 PTGES 的蛋白和 mRNA 表达均显著增加。结果表明，BDE-100 和-209 通过增加 COX-2 和 PTGES 表达来增加前列腺素 E（PGE）的产生。只有 BDE-100 增加了前列腺素 E 受体 EP4 的表达水平，而 BDE-47 和 BDE-209 则降低了其表达水平。这可能解释了为什么仅在暴露于 BDE-47 和 BDE-209 时才会发现对抗炎细胞因子表达水平的抑制作用，而不是在暴露于 BDE-100 时。结果表明，PBDEs 通过触发 PGE-EPs-cAMP-细胞因子信号通路刺激先天免疫反应。
