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Lipids, Lungs, and Livestock: An Exploration of How Omega-3 Fatty Acid-Derived Mediators Impact Airway Inflammation and Carcinogenesis

  • Author(s): Dominguez, Edward C
  • Advisor(s): Talbot, Prue
  • et al.
Creative Commons 'BY' version 4.0 license
Abstract

Exposure to agricultural organic dusts have been well-documented to increase the risk of acute and chronic lung disease among individuals working in the farming and livestock industries. Particulates in organic dust, as well as gaseous compounds in some environments, are what contribute to the lung inflammation elicited upon exposure. As individuals in these industries are exposed to longer durations of agricultural organic dust, the risk increases for the development of chronic lung diseases, such as bronchitis, COPD, and cancer. In addition, these food deserts face restricted access to healthier dietary selections which can be directly correlated to their occupation and lower socioeconomic status. Although the farming industries have access to personal protective equipment, such as masks and ventilators to protect against exposures to dust, they are not always used and as such, additional intervention strategies to protect against these exposures are needed. Omega-3 polyunsaturated fatty acids, such as docosahexaenoic acid (DHA), and their corresponding bioactive-lipid mediators, including resolvin D1 (RvD1), have been shown in the literature to elicit anti-inflammatory and pro-resolving properties making them a unique choice as a therapeutic strategy. The work presented in this dissertation identified the use of a DHA-rich diet as an effective intervention strategy to preemptively dampen a single dust-induced intranasal challenge in mice, providing evidence that dietary supplementation with omega-3 fatty acids is efficient for mitigating the acute inflammatory effects associated with agricultural organic dust exposure. Furthermore, we present data supporting the hypothesis that chronic exposure to agricultural organic dust enhances lung carcinogenesis in mice as well as promotes metastatic properties including epithelial to mesenchymal transition within human lung adenocarcinoma cells. Moreover, this project provides evidence for the therapeutic use of RvD1’s synthetic epimer, aspirin-triggered resolvin D1, for mitigating chronic lung inflammatory responses induced by organic dust. These outcomes are evidenced by reduced leukocyte recruitment, altered oxylipin levels in the lungs, and dampened lung tissue histopathology. Overall, the data presented in this dissertation support the use of omega-3 fatty acid dietary supplementation and administration of their bioactive lipid mediators as potential therapeutic intervention strategies for alleviating the negative acute and chronic lung inflammatory effects of agricultural organic dust exposure among livestock and other farming occupations.

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