Date of Award:
Master of Science (MS)
Animal, Dairy, and Veterinary Sciences
Roger A. Coulombe, Jr.
Roger A. Coulombe, Jr.
Worldwide, exposure to air pollution is a serious human health threat. Particulate matter (PM) air pollution is a mixture of suspended solid and/or liquid particles and particle size is determined by its aerodynamic diameter. Fine, or “respirable” particles, typically from vehicle emissions, manufacturing, power generation, agriculture, as well as secondary photochemical reactions, are classified as ≤2.5μm in diameter (PM2.5). Upon inhalation, PM2.5 particles can reach the lower, more sensitive regions of the lung, enter the bloodstream, and be distributed to other areas in the body. Large-scale epidemiology studies have shown that PM2.5 air pollution is associated with increases in all-cause mortality, cardiopulmonary and cardiovascular disease, stroke, cancer, and Alzheimer’s disease. The normally picturesque Cache Valley of Northern Utah frequently experiences some of the highest PM2.5 concentrations in the United States during inversion events in the winter months. Elevated wintertime PM2.5 concentrations in Cache Valley are primarily due to a combination of human activity and environmental factors. However, the exact mechanism(s) of Cache Valley PM2.5 (CVPM) toxicity, or how CVPM may affect the health of Cache Valley residents, are not fully understood. Previous studies from our laboratory showed that CVPM exposure in cultured human lung cells is associated with the inflammatory response, endoplasmic reticulum (ER) stress, and the unfolded protein response (UPR), a well-known stress-response system in cells. The purpose of this study was to confirm our previous findings since our method for collecting local CVPM was updated to a more effective particle collection system. In the present study, next-generation RNA sequencing revealed that human lung cells exposed to CVPM had gene expression changes related to activation of the UPR. Disruptions in normal cell conditions, or homeostasis, were also observed. Identification of the UPR as an operative mechanism of PM2.5 toxicity will represent an important breakthrough in our understanding of pollutant toxicology because activation of the UPR has been linked to many serious diseases, such as diabetes, retinal degeneration, metabolic disease, and even cancer. My research is also significant because it will enable more accurate risk estimates of CVPM exposure and may help guide positive changes in government regulations to improve air quality.
Eggleston, Morgan, "Differential Transcriptome Analysis Reveals that Cache Valley PM2.5 Triggers the Unfolded Protein Response in Human Lung Cells" (2022). All Graduate Theses and Dissertations. 8408.
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