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Amorphous Silica Nanoparticles Obtained by Laser Ablation Induce Inflammatory Response in Human Lung Fibroblasts.

ABSTRACT: Silica nanoparticles (SiO₂ NPs) represent environmentally born nanomaterials that are used in multiple biomedical applications. Our aim was to study the amorphous SiO₂ NP-induced inflammatory response in MRC-5 human lung fibroblasts up to 72 hours of exposure. The intracellular distribution of SiO₂ NPs was measured by transmission electron microscopy (TEM). The lactate dehydrogenase (LDH) test was used for cellular viability evaluation. We have also investigated the lysosomes formation, protein expression of interleukins (IL-1β, IL-2, IL-6, IL-8, and IL-18), COX-2, Nrf2, TNF-α, and nitric oxide (NO) production. Our results showed that the level of lysosomes increased in time after exposure to the SiO₂ NPs. The expressions of interleukins and COX-2 were upregulated, whereas the expressions and activities of MMP-2 and MMP-9 decreased in a time-dependent manner. Our findings demonstrated that the exposure of MRC-5 cells to 62.5 µg/mL of SiO₂ NPs induced an inflammatory response.

SUBMITTER: Voicu SN

PROVIDER: S-EPMC6479987 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundRecent studies indicate amorphous silica nanoparticles (SiNPs), one of the widely applied nanomaterials, have potential toxicity in humans and induces cell malignant transformation. However, its carcinogenic mechanisms remain poorly understood. This study's purpose was to investigate the underlying toxic mechanisms of amorphous SiNPs on human lung epithelial cells model by using microarray data.MethodsMicroarray dataset GSE82062 was collected from Gene Expression Omnibus database, including three repeats of Beas-2B exposed to amorphous SiNPs for 40 passages and three repeats of passage-matched control Beas-2B cells. Differentially expressed genes (DEGs) were identified using linear models for microarray data method. Protein-protein interaction (PPI) network was constructed using data from the STRING database followed by module analysis. The miRwalk2 database was used to predict the underlying target genes of differentially miRNAs. Function enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID) online tool.ResultsA total of 323 genes were identified as DEGs, including 280 downregulated (containing 12 pre-miRNAs) and 43 upregulated genes (containing 29 pre-miRNAs). Function enrichment indicated these genes were involved in translational initiation (i.e., eukaryotic translation initiation factor 4 gamma 2 (EIF4G2), poly (A) binding protein cytoplasmic 1 (PABPC1)), response to reactive oxygen species (i.e., superoxide dismutase 1 (SOD1)) and oxidative phosphorylation (i.e., ATP5H). PABPC1 (degree = 15), ATP5H (degree = 11) and SOD1 (degree = 8)] were proved to be hub genes after PPI-module analyses. ATP5H/SOD1 and EIF4G2/PABPC1 were overlapped with the target genes of differentially expressed pre-miR-3648/572/661 and pre-miR-4521.ConclusionsAmorphous SiNPs may induce tumorigenesis via influencing ATP5H/SOD1-related oxidative stress, oxidative phosphorylation and EIF4G2/PABPC1-associated translational initiation which may be regulated by miR-3648/572/661 and miR-4521, respectively.

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Amorphous Silica Nanoparticles Obtained by Laser Ablation Induce Inflammatory Response in Human Lung Fibroblasts.

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