Department of Toxicology and Molecular Epidemiology, Institute of Experimental Medicine CAS, Prague, Czech Republic.
Department of Computer Science, Czech Technical University in Prague, Prague, Czech Republic.
Environ Toxicol Pharmacol. 2024 Jun;108:104469. doi: 10.1016/j.etap.2024.104469. Epub 2024 May 15.
We analyzed gene expression in THP-1 cells exposed to metal-based nanomaterials (NMs) [TiO (NM-100), ZnO (NM-110), SiO (NM-200), Ag (NM-300 K)]. A functional enrichment analysis of the significant differentially expressed genes (DEGs) identified the key modulated biological processes and pathways. DEGs were used to construct protein-protein interaction networks. NM-110 and NM-300 K induced changes in the expression of genes involved in oxidative and genotoxic stress, immune response, alterations of cell cycle, detoxification of metal ions and regulation of redox-sensitive pathways. Both NMs shared a number of highly connected protein nodes (hubs) including CXCL8, ATF3, HMOX1, and IL1B. NM-200 induced limited transcriptional changes, mostly related to the immune response; however, several hubs (CXCL8, ATF3) were identical with NM-110 and NM-300 K. No effects of NM-100 were observed. Overall, soluble nanomaterials NM-110 and NM-300 K exerted a wide variety of toxic effects, while insoluble NM-200 induced immunotoxicity; NM-100 caused no detectable changes on the gene expression level.
我们分析了暴露于基于金属的纳米材料（NM）[TiO（NM-100）、ZnO（NM-110）、SiO（NM-200）、Ag（NM-300K）]的 THP-1 细胞中的基因表达。对显著差异表达基因（DEG）的功能富集分析确定了关键的调节生物过程和途径。使用 DEG 构建蛋白质-蛋白质相互作用网络。NM-110 和 NM-300K 诱导与氧化和遗传毒性应激、免疫反应、细胞周期改变、金属离子解毒和氧化还原敏感途径调节相关的基因表达变化。这两种 NM 都有许多高度连接的蛋白质节点（枢纽），包括 CXCL8、ATF3、HMOX1 和 IL1B。NM-200 引起的转录变化有限，主要与免疫反应有关；然而，一些枢纽（CXCL8、ATF3）与 NM-110 和 NM-300K 相同。NM-100 没有观察到效果。总的来说，可溶性纳米材料 NM-110 和 NM-300K 产生了各种各样的毒性作用，而不溶性 NM-200 引起了免疫毒性；NM-100 对基因表达水平没有造成可检测到的变化。
