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Impact of differentiated macrophage-like cells on the transcriptional toxicity profile of cuo nanoparticles in co-cultured lung epithelial cells

Hufnagel, Matthias 1,2,3; Neuberger, Ronja 1,2,3; Wall, Johanna 1,2,3; Link, Martin 1,2,3; Friesen, Alexandra 1,2,3; Hartwig, Andrea 1,2,3
1 Fakultät für Chemie und Biowissenschaften (CHEM-BIO), Karlsruher Institut für Technologie (KIT)
2 Institut für Angewandte Biowissenschaften (IAB), Karlsruher Institut für Technologie (KIT)
3 Institut für Toxikologie und Genetik (ITG), Karlsruher Institut für Technologie (KIT)

Abstract:
To mimic more realistic lung tissue conditions, co-cultures of epithelial and immune cells are one comparatively easy-to-use option. To reveal the impact of immune cells on the mode of action (MoA) of CuO nanoparticles (NP) on epithelial cells, A549 cells as a model for epithelial cells have been cultured with or without differentiated THP-1 cells, as a model for macrophages. After 24 h of submerged incubation, cytotoxicity and transcriptional toxicity profiles were obtained and compared between the cell culture systems. Dose-dependent cytotoxicity was apparent starting from 8.0 µg/cm$^{2}$ CuO NP. With regard to gene expression profiles, no differences between the cell models were observed concerning metal homeostasis, oxidative stress, and DNA damage, confirming the known MoA of CuO NP, i.e., endocytotic particle uptake, intracellular particle dissolution within lysosomes with subsequent metal ion deliberation, increased oxidative stress, and genotoxicity. However, applying a co-culture of epithelial and macrophage-like cells, CuO NP additionally provoked a pro-inflammatory response involving NLRP3 inflammasome and pro-inflammatory transcription factor activation. ... mehr


Verlagsausgabe §
DOI: 10.5445/IR/1000133570
Veröffentlicht am 03.06.2021
Originalveröffentlichung
DOI: 10.3390/ijms22095044
Scopus
Zitationen: 3
Dimensions
Zitationen: 6
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2021
Sprache Englisch
Identifikator ISSN: 1661-6596, 1422-0067
KITopen-ID: 1000133570
Erschienen in International Journal of Molecular Sciences
Verlag MDPI
Band 22
Heft 9
Seiten Art.-Nr.: 5044
Schlagwörter nanotoxicology; co-culture; CuO; A549; THP-1; high-throughput RT-qPCR; gene expression profiles
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Scopus
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