Abstract
Background: In underground railways, airborne particulate matter (PM) concentrations are significantly elevated compared to outdoors. Underground PM is especially rich in iron and transition metals; in the ultrafine fraction (UFPM; diameter
Aim: To analyse cellular responses to underground UFPM beyond the constrained range of markers commonly used.
Methods: UFPM was collected from a European underground station. UFPM-induced antioxidant response element (ARE) activation by the transcription factor Nrf2 was measured in a reporter epithelial cell line transiently transfected with an Nrf2-binding ARE-luciferase construct. Healthy-donor primary bronchial epithelial cells (PBECs) were cultured at air-liquid interface (ALI) to form mucociliary cultures, and exposed to 25µg/ml UFPM for 6h/24h. RNAseq was performed to identify differentially expressed genes (DEGs) following UFPM exposure.
Results: An antioxidant response to underground UFPM was seen with significant activation of ARE after 24h UFPM exposure. In PM-exposed ALI cultures, after 6h there were 52 DEGs (13 up/39 down), particularly associated with epithelial maintenance, whereas after 24h there were 23 DEGs (17 up/6 down), notably relating to redox homeostasis and metal binding. There was prolonged up-regulation of several members of the metal-binding antioxidant metallothionein (MT) family, partially responsive to iron chelation (desferrioxamine) and ROS scavenging (N-acetylcysteine).
Conclusion: These data suggest time-dependent responses to metal-rich UFPM and highlight novel markers of exposure to PM constitutents, such as MTs.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, 284.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
Copyright ©the authors 2019
Aim: To analyse cellular responses to underground UFPM beyond the constrained range of markers commonly used.
Methods: UFPM was collected from a European underground station. UFPM-induced antioxidant response element (ARE) activation by the transcription factor Nrf2 was measured in a reporter epithelial cell line transiently transfected with an Nrf2-binding ARE-luciferase construct. Healthy-donor primary bronchial epithelial cells (PBECs) were cultured at air-liquid interface (ALI) to form mucociliary cultures, and exposed to 25µg/ml UFPM for 6h/24h. RNAseq was performed to identify differentially expressed genes (DEGs) following UFPM exposure.
Results: An antioxidant response to underground UFPM was seen with significant activation of ARE after 24h UFPM exposure. In PM-exposed ALI cultures, after 6h there were 52 DEGs (13 up/39 down), particularly associated with epithelial maintenance, whereas after 24h there were 23 DEGs (17 up/6 down), notably relating to redox homeostasis and metal binding. There was prolonged up-regulation of several members of the metal-binding antioxidant metallothionein (MT) family, partially responsive to iron chelation (desferrioxamine) and ROS scavenging (N-acetylcysteine).
Conclusion: These data suggest time-dependent responses to metal-rich UFPM and highlight novel markers of exposure to PM constitutents, such as MTs.
Footnotes
Cite this article as: European Respiratory Journal 2019; 54: Suppl. 63, 284.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
Copyright ©the authors 2019
Original language | English |
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Number of pages | 1 |
DOIs | |
Publication status | Published - 28 Sept 2019 |