MicroRNA-155 and microRNA-181a, via HO-1, participate in regulating the immunotoxicity of cadmium in the kidneys of exposed Cyprinus carpio

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 Cd2+ 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. •Cd can alter the expressions of immune-related mRNAs and miRNAs in the kidneys of Cyprinus carpio.•Overexpression of miR-155 and knockdown of miR-181a change the immune effects of Cd in Cyprinus carpio.•MiR-155 and miR-181a target HO-1 to regulate the immune response induced by Cd.