Investigation of air pollution interventions in airway epithelial cells
department or school: Medicine, Faculty of
department or school: Medicine, Department of
data provider: DSpace
degree campus: UBCV
creator: Huff, Ryan D.
issued: 2024-02-01T16:24:33Z
issued: 2024
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Air pollution is a pervasive and global problem, with 99% of the world’s population living in areas that exceed the World Health Organization exposure guidelines. Although public policies and legislation continue to lower anthropomorphic emissions, and engineering solutions such as air purifiers work to limit personal exposures, few therapeutic strategies exist to limit the cellular effects of air pollution. To address this issue, I evaluated multiple approaches to counteracting air pollution-induced oxidative stress and inflammation using several in vitro models of particulate matter (PM) exposure on human lung epithelial cells. Using immortalized and primary human epithelial cells exposed to PM, I showed that two antioxidants, tetrahydrocurcumin and quercetin, significantly attenuated cellular reactive oxygen species (ROS) and inflammatory mediator release. Next, I examined the utility of modulating lung epithelial cell responses to PM by priming them with omega-3 fatty acids, precursors of specialised pro-resolving mediators. I demonstrated that docosahexaenoic acid significantly decreased PM-induced pro-inflammatory mediator release and cellular ROS. Finally, I noted that suppressing inflammation in the lungs has been associated with increased susceptibility to viral infections, an association also observed with air pollution exposures. Thus, I investigated the effect of exposing human epithelial cells to air pollution, as well as their treatment with a corticosteroid, a common medication used to control inflammation, on rhinovirus infectivity. I demonstrated that pre-exposure of epithelial cells to the corticosteroid fluticasone propionate and PM synergistically increased rhinovirus levels, suppressed host defence responses, and increased levels of the rhinovirus entry receptor. In summary, this thesis’ investigation of air pollution interventions and possible consequences both provides novel therapeutic options and identifies a potential risk, evidence that co…
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/87399
note: INVESTIGATION OF AIR POLLUTION INTERVENTIONS IN AIRWAY EPITHELIAL CELLS by Ryan D. Huff B.M.Sc., The University of Western Ontario, 2011 M.Sc., The University of British Columbia, 2015 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) January 2024 © Ryan D. Huff, 2024 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Investigation of Air Pollution Interventions in Airway Epithelial Cells submitted by Ryan D. Huff in partial fulfilment of the requirements for the degree of Doctor of Philosophy in Experimental Medicine Examining Committee: Christopher Carlsten, Professor, Respiratory Medicine, UBC Supervisor Jeremy Hirota, Assistant Professor, Department of Medicine, McMaster University Supervisory Committee Member William Lockwood, Associate Professor, Pathology and Laboratory Medicine, UBC University Examiner Andrew Sandford, Professor, Medicine, UBC University Examiner Kymberly Gowdy, Associate Professor, Division of Pulmonary, Critical Care and Sleep Medicine, Ohio State University External Examiner Additional Supervisory Committee Members: David Granville, Professor, Pathology and Laboratory Medicine, UBC Supervisory Committee Member Stephan van Eeden, Professor, Medicine, UBC Supervisory Committee Member iii Abstract Air pollution is a pervasive and global problem, with 99% of the world’s population living in areas that exceed the World Health Organization exposure guidelines. Although public policies and legislation continue to lower anthropomorphic emissions, and engineering solutions such as air purifiers work to limit personal exposures, few therapeutic strategies exist to limit the cellular effects of air pollution. To address this issue, I evaluated multiple approaches t…
has type: Thesis/Dissertation
date issued: 2024-05
is shown at: 10.14288/1.0439328
language: eng
degree discipline: Experimental Medicine
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
contributor: Carlsten, Christopher Russell
type: Text
identifier URI: http://hdl.handle.net/2429/87399