Wang Huili, Li Xin, Wang Weiwei, Xu Jiaqi, Ai Weiming, Huang Haishan, Wang Xuedong
Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China; School of Environmental Science and Engineering, Suzhou University of Science and Technology, Suzhou, 215009, China.
Zhejiang Provincial Key Laboratory of Medical Genetics, Key Laboratory of Laboratory Medicine, Ministry of Education, China School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
Environ Pollut. 2023 May 15;325:121458. doi: 10.1016/j.envpol.2023.121458. Epub 2023 Mar 17.
Owing to frequent application as a broad-spectrum bactericide, triclocarban (TCC) exposure has raised great concern for aquatic organisms and human health. Herein, based on transcriptome sequencing data analysis of zebrafish, we confirmed that TCC induced oxidative stress and dysimmunity through transcriptional regulation of the related genes. With aid of the Cancer Genome Atlas (TCGA) assembler database, 52 common differentially expressed genes, whose functions were related to immunity, were screened out by virtue of the meta-analysis of pancreatic cancer sample data and differential transcription profiles from TCC-exposed larvae. Acute TCC exposure affected formation of the innate immune cells, delayed mature thymic T-cell development, reduced immunoglobulin M (IgM) levels and promoted excessive release of the pro-inflammatory factors (IL-6, IL-1β and tnfα). Under TCC exposure, the expressions of the genes associated with immune cell abundance in pancreatic cancer were significantly down-regulated, while the levels of ROS were prominently increased in concomitant with suppressed antioxidant activity. Moreover, a series of marker genes (pi3k, nrf2, keap1, ho-1 and nqo1) in the PI3K/Nrf2 antioxidant-stress pathway were abnormally expressed under TCC exposure. Interestingly, vitamin C decreased the malformation and increased the survival rate of 120-hpf larvae and effectively alleviated TCC-induced oxidative stress and immune responses. Overall, TCC exposure induced immunotoxicity and increased the risk of pancreatic cancer by inhibiting the antioxidant capacity of the PI3K/Nrf2 signal pathway. These observations enrich our in-depth understanding of the effects of TCC on early embryonic-larval development and immune damage in zebrafish.
由于三氯生（TCC）作为一种广谱杀菌剂被频繁使用，其暴露对水生生物和人类健康引起了极大关注。在此，基于斑马鱼的转录组测序数据分析，我们证实TCC通过相关基因的转录调控诱导氧化应激和免疫功能紊乱。借助癌症基因组图谱（TCGA）组装数据库，通过对胰腺癌样本数据和TCC暴露幼虫的差异转录谱进行荟萃分析，筛选出52个功能与免疫相关的常见差异表达基因。急性TCC暴露影响先天免疫细胞的形成，延迟成熟胸腺T细胞的发育，降低免疫球蛋白M（IgM）水平，并促进促炎因子（IL-6、IL-1β和TNFα）的过度释放。在TCC暴露下，胰腺癌中与免疫细胞丰度相关的基因表达显著下调，而活性氧水平显著升高，同时抗氧化活性受到抑制。此外，PI3K/Nrf2抗氧化应激途径中的一系列标记基因（pi3k、nrf2、keap1、ho-1和nqo1）在TCC暴露下异常表达。有趣的是，维生素C降低了120小时胚胎期幼虫的畸形率并提高了其存活率，并有效减轻了TCC诱导的氧化应激和免疫反应。总体而言，TCC暴露通过抑制PI3K/Nrf2信号通路的抗氧化能力诱导免疫毒性并增加胰腺癌风险。这些观察结果丰富了我们对TCC对斑马鱼早期胚胎-幼虫发育和免疫损伤影响的深入理解。
