Publication Date
2025
Document Type
Thesis
Committee Members
Jeffrey B. Travers, M.D., Ph.D. (Advisor); Mike Kemp, Ph.D. (Committee Member); Ravi P. Sahu, Ph.D. (Committee Member)
Degree Name
Master of Science (MS)
Abstract
Many types of environmental and physical stressors act upon the skin and can initiate inflammation, systemic effects, and even damage to internal organs. Recent studies have identified that these harmful events are driven by the release of subcellular microvesicle particles (MVPs), an inflammatory process promoted by the glycerophosphocholines-derived lipid mediator, Platelet-activating Factor (PAF). These harmful effects are driven by the release of MVPs, a process promoted by the inflammatory lipid mediator, PAF. We have previously demonstrated that exposure of human HaCaT keratinocyte and mouse skin to stressors such as thermal burn injury, ultraviolet B (UVB) radiation, and topical photodynamic therapy (PDT) triggers the release of MVPs. Importantly, thermal burn injury coupled with ethanol intoxication (intoxicated thermal burn injury; ITBI) results in systemic multi-organ dysfunction, facilitated by PAF laden MVPs acting on the gut and inducing bacterial translocation. The goals of the current study are three-fold: 1) To investigate the ability of PDT to initiate MVP release in both HaCaT and murine PAM 212 keratinocyte cell lines; 2) To assess whether cold injury can mediate MVP release and to examine the involvement of PAF and the MVP-generating enzyme acid sphingomyelinase (aSMase) in this process; and 3) To perform “add-back” experiments providing mice with systemic control and ITBI-induced MVPs from human HaCaT cells to determine if they can replicate bacterial translocation like that mediated by ITBI in mice. These studies indicate that multiple stressors could generate MVP and that these MVPs are engaged in systemic effects.
Page Count
32
Department or Program
Department of Pharmacology and Toxicology
Year Degree Awarded
2025
Copyright
Copyright 2025, all rights reserved. My ETD will be available under the "Fair Use" terms of copyright law.
ORCID ID
0009-0004-8626-4660
