College of Fisheries, Engineering Lab of Henan Province for Aquatic Animal Disease Control, Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Henan province, PR China.
College of Fisheries, Engineering Lab of Henan Province for Aquatic Animal Disease Control, Engineering Technology Research Center of Henan Province for Aquatic Animal Cultivation, Henan Normal University, Henan province, PR China.
Fish Shellfish Immunol. 2019 Dec;95:473-480. doi: 10.1016/j.fsi.2019.11.010. Epub 2019 Nov 3.
Cadmium (Cd) is a nonessential metal that is a contaminant in aquatic ecosystems. Cd can accumulate in aquatic animals, leading to detrimental effects in tissues, and Cd exposure can induce immunotoxicity in fish. MicroRNAs (miRNAs) play critical roles in immune responses, yet the participation of miRNAs in Cd-induced immunotoxicity remains poorly understood. The present study evaluated the effects of Cd exposure on the immune responses and the mRNAs and miRNAs expressions of immune-related genes in Cyprinus carpio (C. carpio). Then, microRNA-155 (miR-155) was overexpressed and microRNA-181a (miR-181a) was knocked down to determine which miRNA plays a key role in the immune response to Cd. The results showed that 0.5 mg/L Cd significantly decreased the activity of alkaline phosphatase (AKP) and acid phosphatase (ACP) in the kidneys of C. carpio. Cd exposure upregulated the mRNA expressions of interleukin (IL)-1β, IL-8, nuclear factor-kappa B (NF-κB), tumour necrosis factor-α (TNF-α), and Toll-like receptor 4(TLR-4) and downregulated those of IL-10 and heme oxygenase-1 (HO-1) in C. carpio kidneys. Cd exposure also led to upregulation of miR-155 and miR-181a expressions. Furthermore, AKP and ACP activity in the kidneys was markedly changed after intraperitoneal injection of C. carpio with miR-155 agomir and miR-181a antagomir. All detected mRNA expressions were significantly decreased after injection of miR-155 agomir, and IL-10, NF-κB, TNF-α, and HO-1 mRNA expressions were markedly increased after injection of miR-181a antagomir. The results of this study demonstrate that Cd exposure can immunocompromise C. carpio by targeting HO-1 through miR-155 and miR-181a. This is the first study to reveal that Cd exposure induces immunotoxicity through miR-155 and miR-181a in the kidneys of C. carpio.
镉（Cd）是一种非必需金属，是水生生态系统中的污染物。Cd 可以在水生动物中积累，导致组织损伤，并诱导鱼类的免疫毒性。微小 RNA（miRNA）在免疫反应中发挥关键作用，但 miRNA 参与 Cd 诱导的免疫毒性的机制尚不清楚。本研究评估了 Cd 暴露对鲤鱼（Cyprinus carpio）免疫反应以及免疫相关基因的 mRNA 和 miRNA 表达的影响。然后，过表达 microRNA-155（miR-155）并敲低 microRNA-181a（miR-181a），以确定哪种 miRNA 在对 Cd 的免疫反应中发挥关键作用。结果表明，0.5mg/L Cd 显著降低了鲤鱼肾脏中的碱性磷酸酶（AKP）和酸性磷酸酶（ACP）活性。Cd 暴露上调了鲤鱼肾脏中白细胞介素（IL）-1β、IL-8、核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α）和 Toll 样受体 4（TLR-4）的 mRNA 表达，下调了 IL-10 和血红素加氧酶-1（HO-1）的 mRNA 表达。Cd 暴露还导致 miR-155 和 miR-181a 的表达上调。此外，鲤鱼腹腔注射 miR-155 激动剂和 miR-181a 拮抗剂后，肾脏中的 AKP 和 ACP 活性明显改变。注射 miR-155 激动剂后，所有检测到的 mRNA 表达均显著降低，而注射 miR-181a 拮抗剂后，IL-10、NF-κB、TNF-α和 HO-1 的 mRNA 表达显著增加。本研究结果表明，Cd 通过靶向 HO-1 来损害鲤鱼的免疫系统，这是首次揭示 Cd 暴露通过 miR-155 和 miR-181a 诱导鲤鱼肾脏免疫毒性的研究。
