Intrinsic properties of MWCNT affect immunotoxicity in THP-1 in vitro model
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA910581 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:The immunomodulatory effects seen with exposure to multiwalled carbon nanotubes (MWCNTs) are key events in the progression to pathological outcomes. Therefore, the study of MWCNT induced immunotoxicity is crucial in determining risks posed to human health. MWCNT exposure most commonly occurs via airways, where macrophages are first line responders. Here we exploit an in vitro assay, measuring dose-dependent secretion of a wide panel of cytokines secreted from THP-1 macrophages, as a measure of immunotoxicity following the non-lethal, multi-dose exposure (IC5, IC10 and IC20) to 7 MWCNTs with different intrinsic properties. We find that an underlying tangled structure, and small aspect ratio are key properties predicting MWCNT induced immunotoxicity, mediated predominantly by IL1β cytokine secretion. To assess the mechanism of action giving rise to MWCNT immunotoxicity, a transcriptomics analysis was linked to cytokine secretion in a multilayer model established through correlation across exposure concentrations and time points. This reinforced the finding that tangled MWCNTs have greater immunomodulatory potency, displaying enrichment of immune system, signal transduction and pattern recognition associated pathways. Together our results further elucidate how structure, length and aspect ratio; critical intrinsic properties of MWCNTs, are tied to immunotoxicity.
2023-12-09 | GSE220646 | GEO
Project description:Multi-walled carbon nanotubes (MWCNT) cause lung fibrosis in rodents and exacerbate airway fibrosis in the mouse ovalbumin model of allergic asthma. Interleukin 13 (IL-13) is a key cytokine secreted by T helper type 2 (Th2) cells. IL-13 is up-regulated in human asthma and animal models that activate pro-fibrotic and pro-proliferative cell signaling cascades in human lung fibroblasts (HLF). This study tested the hypothesis that IL-13 alters the gene expression profile of HLF exposed to MWCNT. Carbon black nanoparticles (CBNP) were also compared to MWCNT as they are relatively inert nanoparticles that do not cause fibrosis. Confluent, quiescent cultures of HLF were treated with 10 ng/ml IL-13 or serum-free defined medium (vehicle) for 24 hours prior to treatment with 10 µg/cm2 MWCNT or CBNP. At 4, 24, or 48 hours following nanoparticle exposure, total RNA was isolated and gene expression was measured using the Affymetrix Human Genome U133A2.0 Array. The data were analyzed using the JMP Genomics statistical platform. IL-13 and MWCNT each caused changes in the expression of distinct gene subsets over the time-course investigated. The combination of IL-13 and MWCNT resulted in a gene expression profile that was distinct from patterns induced or suppressed by either IL-13 or MWCNT alone. CBNP caused changes in gene expression that were distinct from IL-13 or MWCNT. Interestingly, the combination of IL-13 and MWCNT increased the expression of IL-17A and increased collagen (Col1A1), while MWCNT alone increased interferon-inducible protein-27 (IFI27), suggesting that Th2 microenvironment containing IL-13 shifts MWCNT-induced gene expression from a Th1 to a Th17 gene expression profile. These data provide insight into the mechanisms by which MWCNT alter the biology of fibroblasts during normal and allergic inflammatory conditions.
2013-05-29 | GSE43515 | GEO
Project description:Pulmonary exposure to multiwalled carbon nanotubes (MWCNT) induces an inflammatory and rapid fibrotic response, although the long-term signaling mechanisms are unknown. The aim of this study was to examine the effects of 1, 10, 40, or 80 μg MWCNT administered by pharyngeal aspiration on bronchoalveolar lavage (BAL) fluid for polymorphonuclear cell (PMN) infiltration, lactate dehydrogenase (LDH) activity, and lung histopathology for inflammatory and fibrotic responses in mouse lungs 1 mo, 6 mo, and 1 yr postexposure. Further, a 120-μg crocidolite asbestos group was incorporated as a positive control for comparative purposes. Results showed that MWCNT increased BAL fluid LDH activity and PMN infiltration in a dose-dependent manner at all three postexposure times. Asbestos exposure elevated LDH activity at all 3 postexposure times and PMN infiltration at 1 mo and 6 mo postexposure. Pathological changes in the lung, the presence of MWCNT or asbestos, and fibrosis were noted at 40 and 80 μg MWCNT and in asbestos-exposed mice at 1 yr postexposure. To identify non-invasive miRNA biomarkers, miRNA profiling was performed in blood samples collected from MWCNT exposed mice.
2019-07-26 | GSE130109 | GEO
Project description:This study compared global multi-walled carbon nanotube (MWCNT)-induced miRNA expression from human lung epithelial and microvascular endothelial cells in monoculture and coculture with miRNA expression from mouse lungs exposed to MWCNT. The concordant miRNA in human cell lines, mouse lung tissues and blood will be potential biomarkers for occupational and medical surveillance.
2022-04-18 | GSE131121 | GEO
Project description:Multi-walled carbon nanotubes (MWCNT) cause lung fibrosis in rodents and exacerbate airway fibrosis in the mouse ovalbumin model of allergic asthma. Interleukin 13 (IL-13) is a key cytokine secreted by T helper type 2 (Th2) cells. IL-13 is up-regulated in human asthma and animal models that activate pro-fibrotic and pro-proliferative cell signaling cascades in human lung fibroblasts (HLF). This study tested the hypothesis that IL-13 alters the gene expression profile of HLF exposed to MWCNT. Carbon black nanoparticles (CBNP) were also compared to MWCNT as they are relatively inert nanoparticles that do not cause fibrosis. Confluent, quiescent cultures of HLF were treated with 10 ng/ml IL-13 or serum-free defined medium (vehicle) for 24 hours prior to treatment with 10 M-BM-5g/cm2 MWCNT or CBNP. At 4, 24, or 48 hours following nanoparticle exposure, total RNA was isolated and gene expression was measured using the Affymetrix Human Genome U133A2.0 Array. The data were analyzed using the JMP Genomics statistical platform. IL-13 and MWCNT each caused changes in the expression of distinct gene subsets over the time-course investigated. The combination of IL-13 and MWCNT resulted in a gene expression profile that was distinct from patterns induced or suppressed by either IL-13 or MWCNT alone. CBNP caused changes in gene expression that were distinct from IL-13 or MWCNT. Interestingly, the combination of IL-13 and MWCNT increased the expression of IL-17A and increased collagen (Col1A1), while MWCNT alone increased interferon-inducible protein-27 (IFI27), suggesting that Th2 microenvironment containing IL-13 shifts MWCNT-induced gene expression from a Th1 to a Th17 gene expression profile. These data provide insight into the mechanisms by which MWCNT alter the biology of fibroblasts during normal and allergic inflammatory conditions. Adult Lung Fibroblasts were treated with 10 M-BM-5g/cm2 MWCNT, CBNP, or vehicle with or without IL-13 for 4 hours, 24 hours, or 48 hours.
2013-05-29 | E-GEOD-43515 | biostudies-arrayexpress
Project description:Multi-walled carbon nanotubes (MWCNT) present a wide variety of exciting application opportunities. As MWCNT are produced in large quantities, occupational exposure and human health is of particular concern. However, there is no consensus regarding their potential harmful effects. In particular, chronic exposure to MWCNT and mechanisms of their action at protein and lipid levels are unknown. In this study, we aimed to investigate effects of long-term chronic exposure to MWCNT on cellular proteome and lipidome. Since the lung is the major target organ, an in vitro normal bronchial epithelial cell model was used. To better mimic exposure at occupational settings, cells were chronically exposed for 13 weeks to low-doses of MWCNT. MWCNT-treatment increased ROS levels in cells without increasing DNA damage and resulted in differential expression of multiple apoptotic proteins. A shotgun proteomic and lipidomic analysis of the MWCNT-exposed cells showed that of amongst the >5000 identified protein s,groups; more than 200 were altered in treated cells. Functional analysis revealed association of these differentially regulated proteins in various cellular processes such as cell death and survival, cellular assembly and organization. Similarly, the lipid profile of the MWCNT treated cells showed accumulation of multiple lipid classes. This is first study to present results indicating that long-term MWCNT-exposure of human normal lung cells at occupationally relevant low-dose may alter both the proteome and the lipidome profile of target epithelial cells in the lung.
2020-05-06 | PXD005970 | Pride
Project description:miRNA profiling of MWCNT exposed mice
| PRJNA542675 | ENA
Project description:Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) is established to cause local acute and chronic inflammation, fibroproliferative responses, immunotoxicity, and systemic responses in rodent studies. However, the search for representative biomarkers of exposure is an ongoing endeavor. Whole blood gene expression profiling is a promising new approach for the identification of novel disease biomarkers over more invasive methods. We asked if the whole blood transcriptome reflects pathology-specific changes in lung gene expression caused by aspiration of MWCNT. To answer this question, we performed mRNA sequencing analysis of the whole blood and lung tissue in a murine model of MWCNT bolus pharyngeal aspiration.
2020-03-03 | GSE140674 | GEO
Project description:Pulmonary exposure to multi-walled carbon nanotubes (MWCNT) is established to cause local acute and chronic inflammation, fibroproliferative responses, immunotoxicity, and systemic responses in rodent studies. However, the search for representative biomarkers of exposure is an ongoing endeavor. Whole blood gene expression profiling is a promising new approach for the identification of novel disease biomarkers over more invasive methods. We asked if the whole blood transcriptome reflects pathology-specific changes in lung gene expression caused by aspiration of MWCNT. To answer this question, we performed mRNA sequencing analysis of the whole blood and lung tissue in a murine model of MWCNT bolus pharyngeal aspiration.
2020-03-03 | GSE140675 | GEO
Project description:coculture SAEC and HMVEC exposed to MWCNT
| PRJNA542679 | ENA