TY - JOUR
T1 - The in vitro immunomodulatory effect of multi-walled carbon nanotubes by multilayer analysis
AU - Hautanen, Veera
AU - Morikka, Jack
AU - Saarimäki, Laura Aliisa
AU - Bisenberger, Jan
AU - Toimela, Tarja
AU - Serra, Angela
AU - Greco, Dario
N1 - Funding Information:
This work received funding from the EU Horizon 2020 project NanoinformaTIX (grant agreement no. 814426 ), the Academy of Finland (grant agreement no. 322761 ), and the European Research Council (ERC) programme, Consolidator project ARCHIMEDES (grant agreement no. 101043848 ). A.S. was supported by the Tampere Institute for Advanced Study .
Funding Information:
This work received funding from the EU Horizon 2020 project NanoinformaTIX (grant agreement no. 814426), the Academy of Finland (grant agreement no. 322761), and the European Research Council (ERC) programme, Consolidator project ARCHIMEDES (grant agreement no. 101043848). A.S. was supported by the Tampere Institute for Advanced Study. The authors would further like to thank Marika Mannerström for her information on THP-1 cell culture and Pia Kinaret and Altoma Rashed for their recommendations in the planning of the study and Altoma Rashed for providing the NM400 and NM401 MWCNTs.
Publisher Copyright:
© 2023 The Authors
PY - 2023/7
Y1 - 2023/7
N2 - The study of multi-walled carbon nanotube (MWCNT) induced immunotoxicity is crucial for determining hazards posed to human health. MWCNT exposure most commonly occurs via the airways, where macrophages are first line responders. Here we exploit an in vitro assay, measuring dose-dependent secretion of a wide panel of cytokines, 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 a tangled structure, and small aspect ratio are key properties predicting MWCNT induced immunotoxicity, mediated predominantly by IL1B cytokine secretion. To assess the mechanism of action giving rise to MWCNT immunotoxicity, transcriptomics analysis was linked to cytokine secretion in a multilayer model established through correlation analysis across exposure concentrations. 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.
AB - The study of multi-walled carbon nanotube (MWCNT) induced immunotoxicity is crucial for determining hazards posed to human health. MWCNT exposure most commonly occurs via the airways, where macrophages are first line responders. Here we exploit an in vitro assay, measuring dose-dependent secretion of a wide panel of cytokines, 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 a tangled structure, and small aspect ratio are key properties predicting MWCNT induced immunotoxicity, mediated predominantly by IL1B cytokine secretion. To assess the mechanism of action giving rise to MWCNT immunotoxicity, transcriptomics analysis was linked to cytokine secretion in a multilayer model established through correlation analysis across exposure concentrations. 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.
KW - Immunotoxicity
KW - In vitro model
KW - Macrophage
KW - Multi-walled carbon nanotube
KW - THP-1
U2 - 10.1016/j.impact.2023.100476
DO - 10.1016/j.impact.2023.100476
M3 - Article
AN - SCOPUS:85164705771
SN - 2452-0748
VL - 31
JO - NanoImpact
JF - NanoImpact
M1 - 100476
ER -
