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Pulmonary Inflammation, Aerosol Exposure, and Health Impacts

Abstract

The work described in this dissertation delves into the intricate relationship between environmental exposures, inflammation, and pulmonary health, with a focus on the impact of chronic exposure to environmental particulate matter from the Salton Sea, TGF-β signaling in allergic asthma, and the therapeutic potential of antimicrobial peptides.

The Salton Sea is California’s largest inland lake, bordering Riverside and Imperial Counties. The impoverished communities surrounding the lake have been documented to suffer from abnormally high rates of asthma. My studies investigated the effects of aerosolized particulate matter from the Salton Sea on pulmonary health. Using a novel aerosol exposure chamber system, I generated murine models to understand the health impacts of chronic particulate matter exposure. My research revealed that exposure to Salton Sea dust elicited distinct inflammatory and gene expression profiles in the lungs. Mice exposed to the dust showed elevated levels of pro-inflammatory cytokines and significant gene expression changes. My studies identified the bacterial toxin, Lipopolysaccharide (LPS), in the dust, linking environmental degradation to public health issues. I found that endotoxins produced by bacteria entrained in the dust triggered severe neutrophilic inflammatory responses in the respiratory system.

In my research on TGF-β signaling, I demonstrated that Vactosertib, a TGF-β RI antagonist, significantly reduces eosinophil recruitment and lung tissue fibrosis. Mice treated with Vactosertib exhibited reduced airway hyperresponsiveness and inflammation compared to untreated controls. These findings underscore the potential of targeted molecular therapies in managing chronic inflammatory diseases and suggest that Vactosertib could be a promising treatment for severe allergic asthma.

Finally, my exploration of antimicrobial peptides from the HLB-resistant Australian Finger Lime revealed their potential as a sustainable alternative to traditional antibiotics. My research showed that these peptides exhibited promising bacteriostatic effects against pathogens such as Salmonella typhimurium and Pseudomonas aeruginosa. By disrupting bacterial cell membranes and affecting biofilm formation, these peptides demonstrated significant bacterial growth inhibition, offering a new avenue for combating resistant pathogens.

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