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Status |
Public on Dec 09, 2023 |
Title |
Intrinsic properties of MWCNT affect immunotoxicity in THP-1 in vitro model |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
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.
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Overall design |
The gene expression profiles of THP-1 macrophages exposed to three concentrations (IC5, IC10 and IC20) of multi-walled carbon nanotubes were profiled at 24 hours. Each concentration had three biological replicates, while only two untreated negative controls from the same plate as the exposures were used. Contributor: Saarimäki
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Contributor(s) |
Hautanen V, Morikka J, Serra A, Bisenberger J, Toimela T, Greco D |
Citation missing |
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Submission date |
Dec 09, 2022 |
Last update date |
Dec 09, 2023 |
Contact name |
Dario Greco |
E-mail(s) |
dario.greco@tuni.fi
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Organization name |
Tampere University
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Department |
Faculty of Medicine and Health Technology
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Lab |
Finnish Hub for Development and Validation of Integrated Approaches (FHAIVE)
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Street address |
Arvo ylpön Katu 34
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City |
Tampere |
ZIP/Postal code |
33520 |
Country |
Finland |
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Platforms (1) |
GPL20844 |
Agilent-072363 SurePrint G3 Human GE v3 8x60K Microarray 039494 [Feature Number Version] |
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Samples (80)
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Relations |
BioProject |
PRJNA910581 |