Publication Date

2025

Document Type

Thesis

Committee Members

Jeffrey B. Travers, M.D., Ph.D. (Advisor); Michael Kemp, Ph.D. (Committee Member); Ravi P. Sahu, Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Ultraviolet B (UVB) radiation, ranging from 280–315 nm, has been identified as carcinogenic since 1928 and is known to cause skin cancer. Additionally, UVB exposure triggers inflammatory responses, systemic effects, and organ damage. Recent research has discovered that these adverse outcomes are facilitated by the release of microvesicle particles (MVP) via the inflammatory lipid mediator, Platelet-activating Factor (PAF). We have previously demonstrated that sunburn causes skin keratinocytes to release high levels of MVP by activating the PAF receptor (PAFR). These studies were designed to test if these microvesicles enter the bloodstream and travel to various organs, especially the gut, increasing gut permeability with resultant bacterial translocation to the lymph nodes and systemically, leading to organ damage. Previously, our lab demonstrated that the MVP level increases, alongside an increase in bacterial translocation, and levels of proinflammatory cytokines, histological changes, and neutrophil increase in different organs after thermal burn injury (TBI) and intoxicated thermal burn injury (ITBI). Our lab also observed that in vitro studies with HaCaT cells treated with UVB showed increased MVP release compared to untreated cells and in C57/BL6 mice, especially in (Xeroderma Pigmentosum Complementary Group A Knock-out) XPA-/-mice, which was inhibited by functional inhibitors of the acid sphingomyelinase enzyme (FIASMAs) like imipramine. In this study, we reproduced the increased release of MVP in HaCaT cells and in C57/BL6 mice following UVB (Ultraviolet radiation) and observed that MVP releases augments even more in XPA-/- mice with no change in the level of MVPs in PAFR-/-, SMPD-/-, and XPA-/- X PAFR-/- mice. This study using wild-type mice also shows increased bacterial translocation following UVB treatment. Of interest, there was only a slight increase in the levels of proinflammatory cytokines, neutrophilic inflammation in multiple organs, and increased bacterial translocation after treatment with UVB noted in WT (Wild type) mice following UVB irradiation. These studies provide evidence that UVB can trigger the release of MVP, which mediates bacterial translocation from the gut and possible systemic inflammation and organ damage.

Page Count

36

Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded

2025

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