Institute for Health and Consumer Protection, Joint Research Centre, European Commission, Validation of Alternative Methods Unit / EURL ECVAM , via E. Fermi 2749, Ispra VA, Italy.
Nanotoxicology. 2013 Sep;7(6):1095-110. doi: 10.3109/17435390.2012.710658. Epub 2012 Aug 13.
An in vitro human alveolar barrier established by the coculture of epithelial human cell line NCI-H441 with endothelial human cell line ISO-HAS1 was used to evaluate the effects of amorphous silicon dioxide nanoparticles (SiNPs), in the presence or absence of THP-1 cells (monocytes). SiNPs exposure induced production of proinflammatory cytokine and oxidative stress. A high release of TNF-α and IL-8 by epithelial/endothelial cells, potentiated in the presence of THP-1 cells could contribute to the observed downregulation of surfactant proteins A mRNA expression resulting in the damage of the alveolar barrier. The obtained results suggested that in vitro approach can be used to study pulmonary toxicity as long as the applied in vitro model mimics closely the complexity of in vivo situation.
采用人肺上皮细胞系 NCI-H441 与人脐静脉内皮细胞系 ISO-HAS1 共培养建立的体外人肺泡屏障,用于评估无定形二氧化硅纳米颗粒(SiNPs)在有无单核细胞 THP-1 细胞存在的情况下的作用。SiNPs 暴露会诱导促炎细胞因子和氧化应激的产生。上皮/内皮细胞产生的 TNF-α和 IL-8 大量释放,在 THP-1 细胞存在时会增强,这可能导致观察到的表面活性剂蛋白 A mRNA 表达下调,从而导致肺泡屏障损伤。研究结果表明,只要应用的体外模型能紧密模拟体内情况的复杂性,体外方法可用于研究肺毒性。