Trimethyltin chloride (TMT) is a highly toxic organotin pollutant frequently found in aquatic environments, posing a significant threat to the ecological system. The kidney plays a vital role in the body's detoxification processes, and TMT present in the environment tends to accumulate in the kidneys. However, it remained unclear whether exposure to different doses of TMT could induce pyroptosis and immune dysfunction in grass carp kidney cells (CIK cells). For this purpose, after assessing the half‐maximal inhibitory concentration (IC50) of TMT on CIK cells, we established a model for exposure of CIK cells at varying concentrations of TMT. CIK cells were treated with various doses of TMT (2.5, 5, 10 μM) for 24 h. Oxidative stress levels were measured using kits and fluorescence methods, whereas the expression of related genes was verified through western blot and quantitative real‐time PCR (qRT‐PCR). The results indicated that TMT exposure led to oxidative stress, with increased levels of ROS, H2O2, MDA, and GSH, and inhibited activities of T‐AOC, SOD, and CAT. It activated the NF‐κB pathway, leading to the upregulation of NF‐κB p65, NF‐κB p50, GSDMD, NLRP3, ASC, and Caspase‐1. Furthermore, TMT exposure also resulted in increased expression of cytokines (IL‐18, IL‐6, IL‐2, IL‐1β, and TNF‐α) and decreased expression of antimicrobial peptides (LEAP2, HEPC, and β‐defensin). In summary, exposure to TMT induces dose‐dependent oxidative stress that activates the NF‐κB pathway, leading to pyroptosis and immune dysfunction in grass carp CIK cells.

中文翻译：

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暴露于三甲基氯化锡通过氧化应激激活 NF-κB 通路，诱导草鱼 CIK 细胞焦亡和免疫功能障碍


三甲基氯化锡 （TMT） 是一种剧毒的有机锡污染物，常见于水生环境中，对生态系统构成重大威胁。肾脏在身体的排毒过程中起着至关重要的作用，环境中存在的 TMT 往往会在肾脏中积累。然而，目前尚不清楚暴露于不同剂量的 TMT 是否会诱导草鱼肾细胞 （CIK 细胞） 的焦亡和免疫功能障碍。为此，在评估了 TMT 对 CIK 细胞的半数最大抑制浓度 （IC50） 后，我们建立了在不同浓度的 TMT 下暴露 CIK 细胞的模型。用不同剂量的 TMT （2.5 、 5 、 10 μM） 处理 CIK 细胞 24 小时。使用试剂盒和荧光方法测量氧化应激水平，而相关基因的表达通过 western blot 和定量实时 PCR （qRT-PCR） 验证。结果表明，TMT 暴露导致氧化应激，ROS 、 H2O2 、 MDA 和 GSH 水平升高，并抑制 T-AOC 、 SOD 和 CAT 的活性。它激活了 NF-κB 通路，导致 NF-κB p65、NF-κB p50、GSDMD、NLRP3、ASC 和 Caspase-1 的上调。此外，TMT 暴露还导致细胞因子 （IL-18、IL-6、IL-2、IL-1β 和 TNF-α） 的表达增加和抗菌肽 （LEAP2、HEPC 和 β-防御素） 的表达降低。总之，暴露于 TMT 会诱导剂量依赖性氧化应激，从而激活 NF-κB 通路，导致草鱼 CIK 细胞焦亡和免疫功能障碍。