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Carbon nanotubes, but not graphene oxide, trigger chemokine production in primary human macrophages via MyD88 dependent NF-kB Pathway

ABSTRACT: The growing medical application of engineered nanomaterials (ENMs) necessitates better understanding of their molecular toxicity mechanisms governing immune effects. In the present study, a comprehensive mechanistic in vitro assessment of two carbon-based ENMs, single-walled carbon nanotubes (SWCNTs) and graphene oxide (GO), was performed using primary human monocyte-derived macrophages (HMDM) as a model. HMDM were exposed to SWCNTs and GO at concentrations 10–100 µg/ml for 24 h. Toxicity, reactive oxygen species (ROS) production and uptake of ENM by cells was measured. The changes in gene expression profile of HMDM in response to SWCNTs and GO were studied and the key stress response pathways identified. The transcriptomics and pathway enrichment analysis findings were verified by multiplex immunoassay and functional assays.

ORGANISM(S): Homo sapiens

PROVIDER: GSE83516 | GEO | 2017/09/30

SECONDARY ACCESSION(S): PRJNA326243

REPOSITORIES: GEO

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A transcriptomic overview of lung and liver changes one day after pulmonary exposure to graphene and graphene oxide

Project description:This study investigates transcriptomic differences in the lung and liver after pulmonary exposure to two Graphene based materials with similar physical properties, but different surface chemistry. Female C57BL/6 mouse were exposed by a single intratracheal instillation of 0, 18, 54 or 162 μg/mouse of graphene oxide (GO) or reduced graphene oxide (rGO). Pulmonary and hepatic transcriptional changes were compared to identify commonly and uniquely perturbed functions and pathways by GO and rGO. These changes were then related to previously analyzed endpoints. GO exposure induced more differentially expressed genes, affected more functions, and perturbed more pathways compared to rGO, both in the lung and liver.

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Improved Biocompatibility of Amino-functionalized Graphene Oxide in Caenorhabditis elegans

Project description:Graphene oxide (GO) holds high promise for diagnostic and therapeutic applications in nanomedicine but reportedly displays immunotoxicity, underlining the need for developing functionalized GO with improved biocompatibility. Here, we study the adverse effects of GO and amino-functionalized GO (GONH2) during Caenorhabditis elegans development and ageing upon acute or chronic exposure. Chronic GO treatment throughout the C. elegans development causes decreased fecundity and a reduction of animal size, while acute treatment does not lead to any measurable physiological decline. However, RNA-Seq data reveal that acute GO exposure induces innate immune gene expression. The p38 MAP kinase, PMK-1, which is a well-established master regulator of innate immunity, protects C. elegans from chronic GO toxicity, as pmk-1 mutants show reduced tissue-functionality and facultative vivipary. In a direct comparison, GONH2 exposure does not cause detrimental effects in the wild type or in pmk-1 mutants, and the innate immune response is considerably less pronounced. Our work establishes the enhanced biocompatibility of amino-functionalized GO in a whole-organism, emphasizing its potential as biomedical nanomaterial.

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Single-cell mass cytometry reveals the impact of graphene nanomaterials with human primary immune cells

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2017-08-13 | GSE99929 | GEO

RNAseq of primary human monocyte derived macrophages (MDM) and differentiated THP-1 macrophages exposed to graphene-related (nano)materials (GRMs)

Project description:Occupational and consumer exposure to GRMs will increase but their impact on human health is still largely unknown. We sought to perform a transcriptome comparison of the bioresponses of MDM and THP-1 macrophages exposed to 5 or 20 µg/ml graphene oxide (GO) or graphene nanoplatelets (GNP) for 6 and 24 h to capture early and more persistent acute responses. Cristalline silica (DQ) was included as immunotoxic reference material.

2023-02-01 | E-MTAB-10099 | biostudies-arrayexpress

Graphene Oxide Substrate Promotes Neurotrophic Factor Secretion and Survival of Human Schwann-Like Adipose Mesenchymal Stromal Cells - RNAseq

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Expression data from Caenorhabditis elegans exposed to single-walled carbon nanotubes

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Next-generation sequencing reveals differential responses to acute versus long-term exposures to graphene oxide in human lung BEAS-2B cells

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2020-03-06 | GSE146482 | GEO

Next-generation sequencing reveals size-dependent pulmonary impact of thin graphene oxide sheets in mice: towards safe-by-design

Project description:Safety assessment of graphene-based materials (GBMs) including graphene oxide (GO) is essential for their safe use across many sectors of society. In particular, the link between specific material properties and biological effects needs to be further elucidated. Here we compared the effects of lateral dimensions of GO sheets in acute and chronic pulmonary responses after single intranasal instillation in mice. Micrometre-sized GO (1–30 μm) induced stronger pulmonary inflammation than nanometre-sized GO, despite a reduced translocation to the lungs. Genome-wide RNA sequencing also revealed distinct size dependent effects of GO, in agreement with the histopathological results. Although large GO, but not the smallest GO (10–300 nm), triggered the formation of granulomas that persisted up to 90 days, no pulmonary fibrosis was observed. These results could be partly explained by the pattern of size-independent in situ biotransformation of GO, as evidenced by Raman spectroscopy imaging. Our findings demonstrate that lateral dimensions play a fundamental role in the pulmonary response to GO, and suggest that airborne exposure to micrometer sized GO should be avoided in production plant or applications, such as spray coating or painting, where aerosolised dispersions are likely to occur. These results are important for the development of evidence-based risk assessment, and provide information towards the implementation of a safer-by-design approach for GBM enhanced products and applications, for the benefit of workers and end-users.

2020-09-30 | GSE146796 | GEO

Identification of circular RNAs expression pattern in caprine fetal fibroblast cells exposed to a chronic noncytotoxic dose of graphene oxide-silver nanoparticle nanocomposites

Project description:circRNA sequencing for 6 samples.The increasing use of graphene oxide-silver nanoparticle nanocomposites (GO-AgNPs) in biomedical sciences and research also increases the chances of human and animal exposure to its chronic non-toxic doses. However, the available information is truly little for profound understanding of the effect of low-dose chronic exposure to GO-AgNPs on the epigenetic modification of the organism. In this research, we have investigated the impact of non-toxic doses of GO-AgNPs (0.5 µg/mL for 10 weeks, this dose does not interfere cell viability and ROS level) on the differential expression of circular RNAs (circRNAs) in caprine fetal fibroblast cells (CFFCs). In addition, using bioinformatics tools we have predicted the functions of those differentially expressed circRNAs on CFFCs. Furthermore, we have validated the expression of ten circRNAs using qRT-PCR to ensure the reliability of the sequencing data. The results showed that the differentially expressed circRNAs potentially regulates the GO-AgNPs induced epigenetic toxicity through a regulatory network consisted of circRNAs, miRNAs and mRNAs. Therefore, the inclusion of epigenetics approaches is essential to assess the biosafety level of GO-AgNPs nanomaterials.

2022-03-31 | GSE199594 | GEO

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Project description:Alzheimer’s disease (AD) is the most common form of neurodegenerations, with oligomerization and aggregation of amyloid-β peptides (Aβ) being one of its histopathological hallmarks. Recently, graphene oxide (GO) nanoflakes have attracted significant attention in biomedical fields by suppression of protein aggregation in vitro. However, the impact of GO on aggregated proteins in vivo is poorly understood. In earlier work, we developed a humanized AD model in yeast Saccharomyces cerevisiae by constitutively expressing Aβ42 peptides to mimic the chronic cytotoxicity during AD progression. Here we apply this in vivo model system to investigate the impact of GO on Aβ42 aggregates and cytotoxicity.

2023-09-28 | PXD029382 | Pride

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