Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117594, Singapore.
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117594, Singapore.
Chem Biol Interact. 2018 Jun 1;289:81-89. doi: 10.1016/j.cbi.2018.04.022. Epub 2018 Apr 26.
Gold nanoparticles (AuNPs) have emerging applications in biomedicine and the industry. Exposure to AuNPs has previously been shown to alter the transcriptional activity of nuclear factor kappa B (NF-kB), which is known to mediate physiological and pathological processes. This study seeks to provide mechanistic insights into AuNP-induced NF-kB activation in Small Airway Epithelial Cells (SAECs) in vitro. Increased NF-kB transcriptional activity (quantified by the luciferase reporter assay) was observed in AuNP-treated SAECs. Transcriptomic analysis revealed differential expression of 42 genes, which regulate functional processes that include cellular response to stimulus, chemicals and stress as well as immune response. Notably, the gene expression of serum amyloid A1 (SAA1), an acute phase protein and Toll-like receptor 2 (TLR2) were found to be up-regulated. As TLR2 is known to be a functional receptor of SAA1, a co-immunoprecipitation assay was performed. SAA1 was observed to be co-immunoprecipitated with the TLR2 protein and this protein-protein interaction was further supported by in silico computer based protein modeling. The present study suggests that AuNPs may potentially induce SAA1-TLR2-mediated NF-kB transcription factor activation in lung epithelial cells, highlighting that nano-bio interactions could result in biological effects that may affect cells.
金纳米粒子(AuNPs)在生物医药和工业领域的应用日益广泛。先前的研究表明,AuNPs 的暴露会改变核因子 kappa B(NF-kB)的转录活性,而 NF-kB 已知介导生理和病理过程。本研究旨在提供机制性的见解,探讨 AuNP 在体外诱导小气道上皮细胞(SAECs)中 NF-kB 激活的机制。AuNP 处理的 SAECs 中观察到 NF-kB 转录活性增加(通过荧光素酶报告基因测定定量)。转录组分析显示,42 个基因的表达存在差异,这些基因调节包括细胞对刺激、化学物质和应激的反应以及免疫反应等功能过程。值得注意的是,血清淀粉样蛋白 A1(SAA1)和 Toll 样受体 2(TLR2)的基因表达上调。由于已知 TLR2 是 SAA1 的功能性受体,因此进行了共免疫沉淀测定。观察到 SAA1 与 TLR2 蛋白共免疫沉淀,并且这种蛋白质-蛋白质相互作用通过基于计算机的蛋白质建模进一步得到支持。本研究表明,AuNPs 可能在肺上皮细胞中诱导 SAA1-TLR2 介导的 NF-kB 转录因子激活,这表明纳米-生物相互作用可能导致影响细胞的生物学效应。