Interdisciplinary Program of Toxicology, Texas A&M University, College Station, TX 77843, United States.
Toxicol Lett. 2012 May 5;210(3):293-301. doi: 10.1016/j.toxlet.2012.01.022. Epub 2012 Feb 9.
There are many efforts in understanding the effects of nanoparticles on cell viability and metabolism, however, not much is known regarding the distinct molecular mechanisms of inflammation and cellular stress using low dosing concentrations. To address this gap in the literature, we utilized a novel experimental design that specifically probes the effects of a panel of commonly studied engineered nanomaterials along immunomodulatory pathways, including NF-κB. The panel of particles selected for this study included quantum dot nanocrystals, titanium dioxide, hydroxylated fullerenes, and silver nanoparticles. Cell viability, antioxidant activity, select messenger RNA, and protein modulation were studied in primary human dermal fibroblasts (HDF) and NF-κB knockdown HDF cells. Inflammatory and non-inflammatory immune responses were measured using protein and real-time PCR array analysis from HDF cells exposed to sub-lethal concentrations of nanoparticles. Differences in cellular response to nanoparticles in protein and antioxidant experiments were evident in NF-κB knockdown cells. The methods used in the study, along with the resultant data sets, serve as a potential model for studying the complex pathway-specific biochemical responses in cell and tissue systems associated with nanoparticle exposures.
尽管人们在了解纳米粒子对细胞活力和代谢的影响方面付出了很多努力,但对于低剂量浓度下炎症和细胞应激的独特分子机制却知之甚少。为了弥补这一文献空白,我们采用了一种新的实验设计,专门研究了一组常见的工程纳米材料沿免疫调节途径的影响,包括 NF-κB。本研究选择的粒子组包括量子点纳米晶体、二氧化钛、羟基化富勒烯和银纳米粒子。在原代人真皮成纤维细胞(HDF)和 NF-κB 敲低 HDF 细胞中研究了细胞活力、抗氧化活性、选择信使 RNA 和蛋白质调节。使用蛋白质和实时 PCR 阵列分析从暴露于亚致死浓度纳米粒子的 HDF 细胞中测量了炎症和非炎症免疫反应。在 NF-κB 敲低细胞中,纳米粒子对蛋白质和抗氧化实验的细胞反应差异明显。该研究中使用的方法以及由此产生的数据集可用作研究与纳米颗粒暴露相关的细胞和组织系统中复杂的特定途径生化反应的潜在模型。