Open Collections

Huff, Ryan D.

University of British Columbia

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 collectively may inform comprehensive strategies to mitigate the risk associated with air pollution exposure.

Text

2024-02-01

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/87399

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/