Publication Date

2019

Document Type

Thesis

Committee Members

Jeffrey B. Travers (Advisor), Michael G. Kemp (Committee Member), Ji Chen Bihl (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Microvesicle particles (MVPs) are subcellular particles that could be involved in inter-cellular communication because they carry various bioactive substances including cytokines. Previous studies from our lab has shown that that the lipid mediator Platelet-activating Factor (1-alkyl-2-acetyl-glycerophosphocholine; PAF) and ultraviolet B radiation (UVB) enhances the release of MVP in various cell types like primary keratinocytes, epithelial cell lines, and murine skin. We hypothesized that there may be synergistic increases in MVP release after combination of treatment of keratinocytes with UVB and PAF agonist (CPAF)/phorbol ester (PMA). The combination treatment significantly increases MVP and cytokine release at 4 to 8 hours time points. Imipramine, an acid sphingomyelinase (aSMase) inhibitor blocks MVP and cytokine release which indicates that MVP could be involved in cytokine release. The increased level of TNF-alpha in the supernatant was not present in the MVP but surprisingly there was increased level of anti-inflammatory cytokine, Interleukin 1- receptor antagonist (IL-1ra) inside MVP after UVB treatment than in combination treatment, which could portray potential imbalances between pro-inflammatory cytokines and down regulating responses in exaggerated condition. These studies suggest that MVP could play a role in how keratinocytes respond to UVB.

Page Count

137

Department or Program

Department of Pharmacology and Toxicology

Year Degree Awarded

2019

ORCID ID

0000-0002-7368-2589


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