The small airway epithelium as a target for the adverse pulmonary effects of silver nanoparticle inhalation

Chang Guo, Alison Buckley, Timothy Marczylo, Joanna Seiffert, Isabella Romer Roche, James Warren, Alan Hodgson, Kian Fan Chung, Timothy Gant, Rachel Smith, Martin Leonard*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

Experimental modeling to identify specific inhalation hazards for nanomaterials has in the main focused on in vivo approaches. However, these models suffer from uncertainties surrounding species-specific differences and cellular targets for biologic response. In terms of pulmonary exposure, approaches which combine ‘inhalation-like’ nanoparticulate aerosol deposition with relevant human cell and tissue air–liquid interface cultures are considered an important complement to in vivo work. In this study, we utilized such a model system to build on previous results from in vivo exposures, which highlighted the small airway epithelium as a target for silver nanoparticle (AgNP) deposition. RNA-SEQ was used to characterize alterations in mRNA and miRNA within the lung. Organotypic-reconstituted 3D human primary small airway epithelial cell cultures (SmallAir) were exposed to the same spark-generated AgNP and at the same dose used in vivo, in an aerosol-exposure air–liquid interface (AE-ALI) system. Adverse effects were characterized using lactate, LDH release and alterations in mRNA and miRNA. Modest toxicological effects were paralleled by significant regulation in gene expression, reflective mainly of specific inflammatory events. Importantly, there was a level of concordance between gene expression changes observed in vitro and in vivo. We also observed a significant correlation between AgNP and mass equivalent silver ion (Ag+) induced transcriptional changes in SmallAir cultures. In addition to key mechanistic information relevant for our understanding of the potential health risks associated with AgNP inhalation exposure, this work further highlights the small airway epithelium as an important target for adverse effects.

Original languageEnglish
Pages (from-to)539-553
Number of pages15
JournalNanotoxicology
Volume12
Issue number6
DOIs
Publication statusPublished - 3 Jul 2018

Bibliographical note

Funding Information:
The original in vivo study was part funded by grants from US National Institute for Environmental Health Sciences grant number [U19ES019536] (http://www.niehs.nih.gov/research/supported/index.cfm), and from the UK National Environmental Research Council grant [NE/H012893] (http://www.nerc.ac.uk/research/). Transcriptomic analysis of lung tissue samples was funded by Public Health England. The in vitro aspect of this research was part funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Health Impact of Environmental Hazards at King?s College London in partnership with Public Health England. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England.

Funding Information:
The original in vivo study was part funded by grants from US National Institute for Environmental Health Sciences grant number [U19ES019536] (http://www.niehs.nih.gov/research/ supported/index.cfm), and from the UK National Environmental Research Council grant [NE/H012893] (http:// www.nerc.ac.uk/research/). Transcriptomic analysis of lung tissue samples was funded by Public Health England. The in vitro aspect of this research was part funded by the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Health Impact of Environmental Hazards at King’s College London in partnership with Public Health England. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, the Department of Health or Public Health England.

Publisher Copyright:
© 2018, © 2018 British Crown Copyright, the Met Office. Published by Informa UK Limited, trading as Taylor & Francis Group.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • Small airway
  • genomics
  • inflammation
  • mechanistic toxicology

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