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Pro-inflammatory effects of crystalline- and nano-sized non-crystalline silica particles in a 3D alveolar model

Authors
  • Skuland, Tonje1
  • Låg, Marit1
  • Gutleb, Arno C.2
  • Brinchmann, Bendik C.1, 3
  • Serchi, Tommaso2
  • Øvrevik, Johan1, 4
  • Holme, Jørn A.1
  • Refsnes, Magne1
  • 1 Norwegian Institute of Public Health, Oslo, N-0403, Norway , Oslo (Norway)
  • 2 Luxembourg Institute of Science and Technology (LIST), Belvaux, Grand Duchy of Luxembourg, Luxembourg , Belvaux, Grand Duchy of Luxembourg (Luxembourg)
  • 3 National Institute of Occupational Health, Oslo, Norway , Oslo (Norway)
  • 4 University of Oslo, Oslo, Norway , Oslo (Norway)
Type
Published Article
Journal
Particle and Fibre Toxicology
Publisher
BioMed Central
Publication Date
Apr 21, 2020
Volume
17
Issue
1
Identifiers
DOI: 10.1186/s12989-020-00345-3
Source
Springer Nature
Keywords
License
Green

Abstract

BackgroundSilica nanoparticles (SiNPs) are among the most widely manufactured and used nanoparticles. Concerns about potential health effects of SiNPs have therefore risen. Using a 3D tri-culture model of the alveolar lung barrier we examined effects of exposure to SiNPs (Si10) and crystalline silica (quartz; Min-U-Sil) in the apical compartment consisting of human alveolar epithelial A549 cells and THP-1-derived macrophages, as well as in the basolateral compartment with Ea.hy926 endothelial cells. Inflammation-related responses were measured by ELISA and gene expression.ResultsExposure to both Si10 and Min-U-Sil induced gene expression and release of CXCL8, interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin-1α (IL-1α) and interleukin-1β (IL-1β) in a concentration-dependent manner. Cytokine/chemokine expression and protein levels were highest in the apical compartment. Si10 and Min-U-Sil also induced expression of adhesion molecules ICAM-1 and E-selectin in the apical compartment. In the basolateral endothelial compartment we observed marked, but postponed effects on expression of all these genes, but only at the highest particle concentrations. Geneexpressions of heme oxygenase-1 (HO-1) and the metalloproteases (MMP-1 and MMP-9) were less affected. The IL-1 receptor antagonist (IL-1RA), markedly reduced effects of Si10 and Min-U-Sil exposures on gene expression of cytokines and adhesion molecules, as well as cytokine-release in both compartments.ConclusionsSi10 and Min-U-Sil induced gene expression and release of pro-inflammatory cytokines/adhesion molecules at both the epithelial/macrophage and endothelial side of a 3D tri-culture. Responses in the basolateral endothelial cells were only induced at high concentrations, and seemed to be mediated by IL-1α/β released from the apical epithelial cells and macrophages.

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