Publication Date

2021

Document Type

Thesis

Committee Members

Jeffrey B. Travers, M.D., Ph.D. (Advisor); Mike Kemp, Ph.D. (Committee Member); Ji Chen Bihl, M.D., Ph.D. (Committee Member)

Degree Name

Master of Science (MS)

Abstract

Cytokines play a pivotal role in regulating inflammation, which is a condition that makes the tissue vulnerable to different pathological and physiological conditions. Thus, how cytokines are regulated is an important area of study. Skin that receives ultraviolet B radiation (UVB), a major pro-oxidative stressor, results in the release of multiple cytokines and chemokines like tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. Previous studies from our group and others have demonstrated synergistic release of TNF-alpha when UVB is combined with IL-1 or the lipid mediator Platelet-activating factor (PAF). Of interest, subcellular microvesicle particles (MVP) have been proposed to play an important role in intercellular communication. Moreover, UVB and PAF agonists cause MVP release in keratinocytes. Therefore, we believe that understanding the role of MVP in these inflammatory responses could be insightful for photosensitivity mechanisms and to suppress inflammation. The current study focuses on the combination of low concentrations of PAF agonist and UVB in-vitro and ex-vivo to observe potential synergism in the release of cytokines and MVP. We also studied the effects of acid sphingomyelinase (aSMase) inhibitor imipramine, for its ability to modulate both MVP and cytokine release. The application of aSMase inhibitor inhibited the synergistic response of MVP and cytokines allows us to conclude the potential involvement of MVP in the exaggerated response of cytokines from combining UVB and PAF. These studies have potential relevance in understanding abnormal skin reactions such as photosensitivity.

Page Count

48

Department or Program

Department of Neuroscience, Cell Biology, and Physiology

Year Degree Awarded

2021

ORCID ID

0000-0001-6445-283X


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