Increased interleukin-11 and stress genes in human endothelial and human bronchial epithelial cell lines by silver nanoparticles

Abstract

The ultrafine particle size of nanomaterials is limited to approximately 100 nm, and such a small size has allowed nanomaterials to be used in a variety of ways. Therefore, engineered nanoparticles are being used in various industries, including ceramics, polymers, smart textiles, pharmaceutical products, cosmetics, biomedicine, electronics, paints, chemicals, food, and environmental analysis. Metal nanoparticles that contain gold, silver, iron, zinc, and metal oxides are widely used for their large surface area to volume ratios and their unique physicochemical properties. In particular, silver NPs are in especially wide use in the medical field, where they are used in diagnosis and treatment and incorporated into medical devices and pharmaceuticals. Interestingly, however, silver NPs have been identified as a cause toxicity in the human body. Because of their small size, NPs that enter the human body can easily penetrate biological barriers and can be circulated throughout the entire body, ultimately reaching the vascular endothelium. With this in mind, the present study aimed to identify various cell responses by distinguishing between endothelial and epithelial cells and exposing them to silver nanoparticles (NPs). The study also worked to identify the progression of cell apoptosis that occurs as a result of intracellular oxidative stress caused by silver NPs and to determine which genes are being stimulated in order to cause such changes. We also assessed several gene expression levels that increased significantly in the microarray assay. We evaluated the cytotoxic effects of silver NPs both endothelial and epithelial cells. Although the LD50 of each cell line was estimated differently, we were able to prove the toxicity of silver NPs. Meanwhile, for 100 nm silver NPs, cell death was not observed in the high concentration group. We verified through microarray that 5 nm silver NPs affect the variation of gene expression in cells, and a noticeable increase in the expression of interleukin (IL)-8 and IL-11 genes in early time was also verified. This study found that the variation in oxidative stress-related genes in early time, and among them the variation of metallothionein (MT), heme oxygenase 1 (HO-1), and heat shock 70kDa protein (HSP70) expression, was noticeable. This study proves that HSP70, HO-1, and MT are sufficient as biomarkers of reactive oxygen species (ROS) and that the oxidative stress effect is greater as the size of NPs is smaller assuming that there is no variation in ROS related gene expression in 100 nm silver NPs. The microarray used in this study can analyze up to 24,838 RefSeq (Entrez) genes. Based on this analysis, genes undergoing intracellular change after exposure to silver NPs were classified into five categories: cell death, cell survival, inflammation, apoptosis, and ROS. As a result, there was considerable variation in genes related to cell death and apoptosis, and the expression of genes related to cell survival was also not negligible. Meanwhile, the number of genes related to inflammation was relatively small. Moreover, what is especially worth paying attention to is the increased IL-11 gene expression, which has not been much discussed in previous studies. In this study, the IL-11 gene expression particularly increased following the exposure of endothelial and epithelial cells to 5 nm silver nanoparticles. This study therefore verifies that IL-11 expression commonly increases in cells under the influence of silver NPs. In conclusion, this study finds that intracellular genes specifically respond to exposure to silver NPs and that the expression of IL-11 among cytokines is noticeable. It also finds that the toxic effect is affected by the size of NPs. However, this study verifies only that IL-11 expression increased, and thus further study would be required to elaborate on the various roles played by IL-11.

초미립자 나노물질의 크기는 약100 nm 정도로 이러한 작은 크기의 특성으로 인하여 산업적으로 여러 방면에서 활용이 되고 있다. 그...