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Silica nanoparticles effects on gene expression of A549 cells

ABSTRACT: Expansion of nanotechnology will bring many potential benefits as adversely effects on human health. Protection of the human respiratory system from exposure of volatile nanoparticles has become an emerging health concern. The understanding of the biological processes involved in the development and maintenance of a variety of pathologies is improved by genome-wide approaches. Technical feasibility of this type of experiment has perfected in recent years, but data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. We demonstrate how the use of a combination of gene-by-gene and gene set analyses can enhance the interpretation of results. Gene set analyses are able to distinguish responses due to nanoparticle size also discriminating between long and short time recovery after exposure. Transcription regulation and cell proliferation modulation appear to be an early response while oxidative stress and mitochondrial perturbation are late response. Moreover, smaller the particle higher the effect on inflammatory response and DNA damage activation. By integrating the two approaches, we evidenced the importance of MMP1, MMP9, MMP7 and MMP14 genes in response to Ludox® silica nanoparticles and the involvement apoptosis process in cell viability. This study is based on the treatment of A549 cells with two different silica nanoparticles (SM30, 9 nm of diameter, and AS30, 18 nm of diameter). Treatment with nanoparticles were performed independently. We performed three biological replicates for each condition.

ORGANISM(S): Homo sapiens

SUBMITTER: Fede C

PROVIDER: S-ECPF-GEOD-53700 | biostudies-other | 2014 Sep

REPOSITORIES: biostudies-other

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Silica nanoparticles effects on gene expression of A549 cells

Project description:Expansion of nanotechnology will bring many potential benefits as adversely effects on human health. Protection of the human respiratory system from exposure of volatile nanoparticles has become an emerging health concern. The understanding of the biological processes involved in the development and maintenance of a variety of pathologies is improved by genome-wide approaches. Technical feasibility of this type of experiment has perfected in recent years, but data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. We demonstrate how the use of a combination of gene-by-gene and gene set analyses can enhance the interpretation of results. Gene set analyses are able to distinguish responses due to nanoparticle size also discriminating between long and short time recovery after exposure. Transcription regulation and cell proliferation modulation appear to be an early response while oxidative stress and mitochondrial perturbation are late response. Moreover, smaller the particle higher the effect on inflammatory response and DNA damage activation. By integrating the two approaches, we evidenced the importance of MMP1, MMP9, MMP7 and MMP14 genes in response to Ludox® silica nanoparticles and the involvement apoptosis process in cell viability.

2014-09-08 | GSE53700 | GEO

Silica nanoparticles effects on gene expression of A549 cells

Project description:Expansion of nanotechnology will bring many potential benefits as adversely effects on human health. Protection of the human respiratory system from exposure of volatile nanoparticles has become an emerging health concern. The understanding of the biological processes involved in the development and maintenance of a variety of pathologies is improved by genome-wide approaches. Technical feasibility of this type of experiment has perfected in recent years, but data analysis remains challenging. In this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. We demonstrate how the use of a combination of gene-by-gene and gene set analyses can enhance the interpretation of results. Gene set analyses are able to distinguish responses due to nanoparticle size also discriminating between long and short time recovery after exposure. Transcription regulation and cell proliferation modulation appear to be an early response while oxidative stress and mitochondrial perturbation are late response. Moreover, smaller the particle higher the effect on inflammatory response and DNA damage activation. By integrating the two approaches, we evidenced the importance of MMP1, MMP9, MMP7 and MMP14 genes in response to LudoxÂ® silica nanoparticles and the involvement apoptosis process in cell viability. This study is based on the treatment of A549 cells with two different silica nanoparticles (SM30, 9 nm of diameter, and AS30, 18 nm of diameter). Treatment with nanoparticles were performed independently. We performed three biological replicates for each condition.

2014-09-08 | E-GEOD-53700 | biostudies-arrayexpress

Transcriptional profiling of A549 cells exposed to silica nanoparticles coated by bovine serum albumin

Project description:A549 cells were treated with 130 microgram/ml BSA-coated SiO2 nanoparticles for 24 h.

2012-05-01 | E-MEXP-3600 | biostudies-arrayexpress

Mixture Effects of Diesel Exhaust and Metal Oxide Nanoparticles in Human Lung A549 Cells.

Project description:Airborne ultrafine particles (UFP) mainly derive from combustion sources (e.g., diesel exhaust particles-DEP), abrasion sources (non-exhaust particles) or from the unintentional release of engineered nanoparticles (e.g., metal oxide nanoparticles-NPs), determining human exposure to UFP mixtures. The aim of the present study was to analyse the combined in vitro effects of DEP and metal oxide NPs (ZnO, CuO) on human lung A549 cells. The mixtures and the relative single NPs (DEP, ZnO, CuO) were characterized by transmission electron microscopy (TEM), dynamic light scattering (DLS) and inductively coupled plasma-optic emission spectroscopy (ICP-OES). Cells were exposed for different times (3-72 h) to mixtures of standard DEP at a subcytotoxic concentration and ZnO and CuO at increasing concentrations. At the end of the exposure, the cytotoxicity was assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and clonogenic tests, the pro-inflammatory potential was evaluated by interleukin-8 (IL-8) release and the cell morphology was investigated by fluorescence and transmission electron microscopy. The obtained results suggest that the presence of DEP may introduce new physico-chemical interactions able to increase the cytotoxicity of ZnO and to reduce that of CuO NPs.

| S-EPMC6781047 | biostudies-literature

Macrophage response to silica nanoparticles

Project description:Using a macrophage cell line, we demonstrate the ability of amorphous silica particles to stimulate inflammatory protein secretion and induce cytotoxicity. Whole genome microarray analysis of early gene expression changes induced by 10nm and 500nm particles showed that the magnitude of change for the majority of genes correlated more tightly with particle surface area than either particle mass or number. Gene expression changes that were size-specific were also identified, however the overall biological processes represented by all gene expression changes were nearly identical, irrespective of particle diameter. Our results suggest that on an equivalent nominal surface area basis, common biological modes of action are expected for nano- and supranano-sized silica particles. Keywords: Dose-response study

2008-12-11 | GSE13005 | GEO

Altered gene transcription in human cells treated with Ludox® silica nanoparticles.

Project description:Silica (SiO2) nanoparticles (NPs) have found extensive applications in industrial manufacturing, biomedical and biotechnological fields. Therefore, the increasing exposure to such ultrafine particles requires studies to characterize their potential cytotoxic effects in order to provide exhaustive information to assess the impact of nanomaterials on human health. The understanding of the biological processes involved in the development and maintenance of a variety of pathologies is improved by genome-wide approaches, and in this context, gene set analysis has emerged as a fundamental tool for the interpretation of the results. In this work we show how the use of a combination of gene-by-gene and gene set analyses can enhance the interpretation of results of in vitro treatment of A549 cells with Ludox® colloidal amorphous silica nanoparticles. By gene-by-gene and gene set analyses, we evidenced a specific cell response in relation to NPs size and elapsed time after treatment, with the smaller NPs (SM30) having higher impact on inflammatory and apoptosis processes than the bigger ones. Apoptotic process appeared to be activated by the up-regulation of the initiator genes TNFa and IL1b and by ATM. Moreover, our analyses evidenced that cell treatment with LudoxÒ silica nanoparticles activated the matrix metalloproteinase genes MMP1, MMP10 and MMP9. The information derived from this study can be informative about the cytotoxicity of Ludox® and other similar colloidal amorphous silica NPs prepared by solution processes.

| S-EPMC4198995 | biostudies-literature

Effect of ultra-small silica nanoparticles (USSNs) on gene expression of peripheral blood mononuclear cells

Project description:Humans are exposed to high levels of amorphous silica particles daily, as they are used in food, cosmetic and pharmaceutical products, and recently in bioclinical applications. Here, peripheral blood mononuclear cells were exposed to USSNs (silicon) and their gene expression was assessed

2018-04-13 | GSE113088 | GEO

Global gene expression analysis of macrophage response induced by nonporous and porous silica nanoparticles.

Project description:Little is known about the global gene expression profile of macrophages in response to changes in size and porosity of silica nanoparticles (SNPs). Spherical nonporous SNPs of two different diameters, and mesoporous spherical SNPs with comparable size were characterized. Reactive oxygen species, mitochondrial membrane potential, lysosome degradation capacity, and lysosome pH were measured to evaluate the influence of nonporous and mesoporous SNPs on mitochondrial and lysosomal function. RNA-sequencing was utilized to generate transcriptional profiles of RAW264.7 macrophages exposed to non-toxic SNP doses. DESeq2, limma, and BinReg2 software were used to analyze the data based on both unsupervised and supervised strategies to identify genes with greatest differences among NP treatments. Utilizing GATHER and DAVID software, possible induced pathways were studied. We found that mesoporous silica nanoparticles are capable of altering gene expression in macrophages at doses that do not elicit acute cytotoxicity, while gene transcription was minimally affected by nonporous SNPs.

| S-EPMC6050981 | biostudies-literature

Titanium Dioxide Nanoparticles Alter the Cellular Phosphoproteome in A549 Cells.

Project description:TiO2 nanoparticles (NPs) are one of the most produced NPs worldwide and are used in many consumer products. Their impact on human health, especially through inhalation, has been studied for more than two decades. TiO2 is known for its strong affinity towards phosphates, and consequently interaction with cellular phosphates may be one of the mechanisms driving its toxicity. In the present study, we used a phosphoproteomics approach to document the interaction of TiO2-NP with phosphoproteins from A549 human pulmonary alveolar epithelial cells. Cells were exposed to 21 nm anatase/rutile TiO2-NPs, then their phosphopeptides were extracted and analyzed using shotgun proteomics. By comparing the phosphoprotein content, phosphorylation status and phosphorylation sites of exposed cells with that of control cells, our results show that by affecting the phosphoproteome, TiO2-NPs affect cellular processes such as apoptosis, linked with cell cycle and the DNA damage response, TP53 being central to these pathways. Other pathways including inflammation and molecular transport are also affected. These molecular mechanisms of TiO2-NP toxicity have been reported previously, our study shows for the first time that they may derive from phosphoproteome modulation, which could be one of their upstream regulators.

| S-EPMC7074930 | biostudies-literature

Gene expression profiling of cancer stem cell in human lung adenocarcinoma A549 cells.

Project description:BackgroundThe studies on cancer-stem-cells (CSCs) have attracted so much attention in recent years as possible therapeutic implications. This study was carried out to investigate the gene expression profile of CSCs in human lung adenocarcinoma A549 cells.ResultsWe isolated CSCs from A549 cell line of which side population (SP) phenotype revealed several stem cell properties. After staining the cell line with Hoechst 33342 dye, the SP and non-side population (non-SP) cells were sorted using flow cytometric analysis. The mRNA expression profiles were measured using an Affymetrix GeneChip(R) oligonucleotide array. Among the sixty one differentially expressed genes, the twelve genes inclusive three poor prognostic genes; Aldo-keto reductase family 1, member C1/C2 (AKR1C1/C2), Transmembrane 4 L six family member 1 nuclear receptor (TM4SF1), and Nuclear receptor subfamily 0, group B, member 1 (NR0B1) were significantly up-regulated in SP compared to non-SP cells.ConclusionThis is the first report indicating the differences of gene expression pattern between SP and non-SP cells in A549 cells. We suggest that the up-regulations of the genes AKR1C1/C2, TM4SF1 and NR0B1 in SP of human adenocarcinoma A549 cells could be a target of poor prognosis in anti-cancer therapy.

| S-EPMC2234429 | biostudies-literature

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