LSC - 2019 - Novel cellular effects of ultrafine particulate matter from an underground railway station uncovered through RNAseq

Matthew Loxham, Jeongmin Woo, Akul Singhania, Natalie Smithers, Alison Yeomans, Graham Packham, Alina Crainic, Richard Cook, Flemming Cassee, Christopher Woelk, Donna Davies

    Research output: Contribution to conferencePaperAcademic

    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
    Original languageEnglish
    Number of pages1
    DOIs
    Publication statusPublished - 28 Sept 2019

    Fingerprint

    Dive into the research topics of 'LSC - 2019 - Novel cellular effects of ultrafine particulate matter from an underground railway station uncovered through RNAseq'. Together they form a unique fingerprint.

    Cite this