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Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [expression]

ABSTRACT: Multi-omics approach to characterize the dynamic dose-dependent (DDD) molecular alterations in a model of human macrophages was used to highlight key-genes altered due to rCNT exposure. Results emphasize short and long term changes in gene regulation, that further suggest fibrotic responses, previously reported in in vivo animal model.

ORGANISM(S): Homo sapiens

PROVIDER: GSE146708 | GEO | 2021/03/05

REPOSITORIES: GEO

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Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [methylation]

Project description:Toxicogenomics approaches are increasingly applied to gain mechanistic insight into the toxicity of engineered nanomaterials (ENMs). These emerging technologies have been shown to aid the translation of in vitro experimentation into relevant information on real-life exposures. Furthermore, integrating multiple layers of molecular alteration can improve the systemic understanding of the toxicological insult. While evidence of the immunotoxic effects of several ENMs is arising, the mechanisms are less characterized, and the dynamics of the molecular adaptation of the immune cells are still largely unknown. Here, we carried out a multi-omics approach characterizing the dynamic dose-dependent (DDD) molecular alterations in a model of human macrophages. THP-1 macrophages were exposed to increasing concentrations of rigid multiwalled carbon nanotubes (rCNTs) and the genome-wide alterations in the transcriptome and gene promoter methylation were assessed at three consecutive time points. The results suggest dynamic patterns of molecular alterations with a rapid response in the gene expression and contribution of DNA methylation in the long-term adaptation. Moreover, our analytical approach is able to highlight patterns of molecular alteration in vitro that recapitulate several elements of pathogenesis of pulmonary fibrosis, a known long-term effect of rCNTs exposure in vivo.

2021-03-05 | GSE146551 | GEO

Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-03-05 | GSE146710 | GEO

Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis

Project description:Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis

| PRJNA611721 | ENA

Lung response to multi-walled carbon nanotube exposure in rats.

Project description:The projected increase in the production and use of nanomaterials is expected to result in a corresponding increase in human exposure, potentially resulting in significant morbidity and mortality. Currently, the lung toxicity of multi-walled carbon nanotubes (MWCNT), a prototype nanomaterial, was investigated in a rat model. The rats were exposed by whole-body inhalation to air (controls) or MWCNT (6 hours/day, 3 days) to result in cumulative doses of 180, 90, 45, 22.5, or 11.25 mg/m3. Lung toxicity and gene expression profiles were determined in the lungs of the control and MWCNT exposed rats one day following termination of the exposures. Moderate lung histological changes, indicative of toxicity, were detected in rats exposed to MWCNT at doses > 45 mg/m3. Changes in toxicity parameters including, lactate dehydrogenase (LDH) activity, oxidant production, cell counts of phagocytes, and cytokine levels were detected in the bronchoalveolar lavage of rats exposed to > 22.5 mg/m3 MWCNT, compared with the air controls. Lung gene expression profiling detected differences in transcript levels (fold change >1.5 and FDR p<0.05) of several genes in the rats exposed to >22.5 mg/m3 MWCNT, compared with the controls. The changes in lung toxicity and gene expression profiles exhibited a dose-response to the MWCNT administered in the rats.

2022-12-31 | GSE148869 | GEO

Multi-walled carbon nanotube-induced gene expression in vitro

Project description:There is a current interest in reducing the in vivo toxicity testing of nanomaterials in animals by increasing toxicity testing using in vitro cellular assays; however, toxicological results are seldom concordant between in vivo and in vitro models. This study compared global multi-walled carbon nanotube (MWCNT)-induced gene expression from human lung epithelial and microvascular endothelial cells in monoculture and coculture with gene expression from mouse lungs exposed to MWCNT. Using a cutoff of 10% false discovery rate and 1.5 fold change, we determined that there were more concordant genes (gene expression both up- or downregulated in vivo and in vitro) expressed in both cell types in coculture than in monoculture. When reduced to only those genes involved in inflammation and fibrosis, known outcomes of in vivo MWCNT exposure, there were more disease-related concordant genes expressed in coculture than monoculture. Additionally, different cellular signaling pathways are activated in response to MWCNT dependent upon culturing conditions. As coculture gene expression better correlated with in vivo gene expression, we suggest that cellular cocultures may offer enhanced in vitro models for nanoparticle risk assessment and the reduction of in vivo toxicological testing.

2019-04-12 | GSE129640 | GEO

Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [methylation]

Project description:Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [methylation]

| PRJNA611710 | ENA

Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [expression]

Project description:Multi-omics analysis of dynamic dose-response in macrophages recapitulates multi-walled carbon nanotube -induced lung fibrosis [expression]

| PRJNA611724 | ENA

Multi-fractal hierarchy of single-walled carbon nanotube hydrophobic coatings.

Project description:A hierarchical structure is an assembly with a multi-scale morphology and with a large and accessible surface area. Recent advances in nanomaterial science have made increasingly possible the design of hierarchical surfaces with specific and tunable properties. Here, we report the fractal analysis of hierarchical single-walled carbon nanotube (SWCNT) films realized by a simple, rapid, reproducible, and inexpensive filtration process from an aqueous dispersion, then deposited by drytransfer printing method on several substrates, at room temperature. Furthermore, by varying the thickness of carbon nanotube random networks, it is possible tailoring their wettability due to capillary phenomena in the porous films. Moreover, in order to describe the wetting properties of such surfaces, we introduce a two-dimensional extension of the Wenzel-Cassie-Baxter theory. The hierarchical surface roughness of SWCNT coatings coupled with their exceptional and tunable optical and electrical properties provide an ideal hydrophobic composite surface for a new class of optoelectronic and nanofluidic devices.

| S-EPMC4341200 | biostudies-literature

Lung carcinogenicity of inhaled multi-walled carbon nanotube in rats.

Project description:BackgroundMulti-walled carbon nanotubes (MWCNTs) constitute one of the most promising types of nanomaterials in industry today. With their increasing use, the potential toxicity and carcinogenicity of MWCNT needs to be evaluated in bioassay studies using rodents. Since humans are mainly exposed to MWCNT by inhalation, we performed a 104-week carcinogenicity study using whole-body inhalation exposure chambers with a fibrous straight type of MWCNT at concentrations of 0, 0.02, 0.2, and 2 mg/m3 using male and female F344 rats.ResultsLung carcinomas, mainly bronchiolo-alveolar carcinoma, and combined carcinomas and adenomas were significantly increased in males exposed to 0.2 and 2 mg/m3 MWNT-7 and in females exposed to 2 mg/m3 MWNT-7 compared to the clean air control group. However, no development of pleural mesothelioma was observed. Concentration-dependent toxic effects in the lung such as epithelial hyperplasia, granulomatous change, localized fibrosis, and alteration in BALF parameters were found in MWNT-7 treatment groups of both sexes. There were no MWNT-7-specific macroscopic findings in the other organs, including the pleura and peritoneum. Absolute and relative lung weights were significantly elevated in male rats exposed to 0.2 and 2 mg/m3 MWNT-7 and in all exposed female groups. The lung burdens of MWNT-7 were clearly increased in a concentration-dependent as well as a duration-dependent manner.ConclusionThere is clear evidence that MWNT-7 is carcinogenic to the lungs of male and female F344 rats, however no plural mesothelioma was observed.

| S-EPMC5064785 | biostudies-literature

Multi-walled carbon nanotube physicochemical properties predict pulmonary inflammation and genotoxicity.

Project description:Lung deposition of multi-walled carbon nanotubes (MWCNT) induces pulmonary toxicity. Commercial MWCNT vary greatly in physicochemical properties and consequently in biological effects. To identify determinants of MWCNT-induced toxicity, we analyzed the effects of pulmonary exposure to 10 commercial MWCNT (supplied in three groups of different dimensions, with one pristine and two/three surface modified in each group). We characterized morphology, chemical composition, surface area and functionalization levels. MWCNT were deposited in lungs of female C57BL/6J mice by intratracheal instillation of 0, 6, 18 or 54??g/mouse. Pulmonary inflammation (neutrophil influx in bronchoalveolar lavage (BAL)) and genotoxicity were determined on day 1, 28 or 92. Histopathology of the lungs was performed on day 28 and 92. All MWCNT induced similar histological changes. Lymphocytic aggregates were detected for all MWCNT on day 28 and 92. Using adjusted, multiple regression analyses, inflammation and genotoxicity were related to dose, time and physicochemical properties. The specific surface area (BET) was identified as a positive predictor of pulmonary inflammation on all post-exposure days. In addition, length significantly predicted pulmonary inflammation, whereas surface oxidation (-OH and -COOH) was predictor of lowered inflammation on day 28. BET surface area, and therefore diameter, significantly predicted genotoxicity in BAL fluid cells and lung tissue such that lower BET surface area or correspondingly larger diameter was associated with increased genotoxicity. This study provides information on possible toxicity-driving physicochemical properties of MWCNT. The results may contribute to safe-by-design manufacturing of MWCNT, thereby minimizing adverse effects.

| S-EPMC5020352 | biostudies-literature

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