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Upregulation of epithelial metallothioneins by metal-rich ultrafine particulate matter from an underground railway

DOI: 10.1039/D0MT00014K DOI Help

Authors: Matthew Loxham (University Hospital Southampton) , Jeongmin Woo (University Hospital Southampton) , Akul Singhania (University Hospital Southampton) , Natalie P. Smithers (University Hospital Southampton) , Alison Yeomans (University Hospital Southampton) , Graham Packham (University Hospital Southampton) , Alina M. Crainic (University of Southampton) , Richard B. Cook (University of Southampton) , Flemming R. Cassee (National Institute for Public Health and the Environment (RIVM)) , Christopher H. Woelk (University Hospital Southampton) , Donna E. Davies (University Hospital Southampton)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Metallomics , VOL 122

State: Published (Approved)
Published: April 2020
Diamond Proposal Number(s): 17801

Open Access Open Access

Abstract: Airborne particulate matter (PM) is a leading cause of mortality and morbidity. However, understanding of the range and mechanisms of effects of PM components is poor. PM generated in underground railways is rich in metals, especially iron. In the ultrafine (UFPM; <0.1 μm diameter) fraction, the combination of small size and metal enrichment poses an unknown health risk. This study aimed to analyse transcriptomic responses to underground UFPM in primary bronchial epithelial cells (PBECs), a key site of PM deposition. The oxidation state of iron in UFPM from an underground station was determined by X-ray absorption near edge structure (XANES) spectroscopy. Antioxidant response was assayed using a reporter cell line transfected with an antioxidant response element (ARE)-luciferase construct. Differentiated PBECs were exposed to UFPM for 6 h or 24 h for RNA-Seq and RT-qPCR analysis. XANES showed predominance of redox-active Fe3O4, with ROS generation confirmed by induction of ARE-luciferase expression. 6 h exposure of PBECs to UFPM identified 52 differentially expressed genes (DEGs), especially associated with epithelial maintenance, whereas 24 h exposure yielded 23 DEGs, particularly involved with redox homeostasis and metal binding. At both timepoints, there was upregulation of members of the metallothionein family, low molecular weight proteins with antioxidant activity whose main function is binding and homeostasis of zinc and copper ions, but not iron ions. This upregulation was partially inhibited by metal chelation or ROS scavenging. These data suggest differential regulation of responses to metal-rich UFPM depending on exposure period, and highlight novel pathways and markers of PM exposure, with the role of metallothioneins warranting further investigation

Subject Areas: Biology and Bio-materials


Instruments: I08-Scanning X-ray Microscopy beamline (SXM)