Publication Date

2024

Document Type

Thesis

Committee Members

Jeffrey B. Traver, Michael George Kemp, Ravi P. Sahu, Paula Bubulya

Degree Name

Master of Science

Abstract

Many diseases including lupus erythematosus, atopic eczema, and rosacea can be associated with photosensitivity, which is an abnormal response to sunlight. Recent studies by our group have implicated microvesicle particles (MVP) as playing an important role in causing inflammation and systemic immunosuppression. Previous studies show that functional inhibitors of acid sphingomyelinase (FIASMA) can block MVP release in response to ultraviolet B (UVB) radiation or Platelet-activating Factor (PAF) agonist, which are skin stressors. However, more research needs to be conducted to evaluate the role of PAF, UVB and FIASMA in MVP generation and to formulate a therapeutic medication to be potentially used to treat photosensitivity. One of the major obstacles is the limited availability of human skin explants for research use. To investigate the mechanism of MVP generation and inhibition, we have proposed a preclinical model, porcine skin explants, as a substitute for human skin explants, which is comparatively easier to procure. In this study, we used one of five different FIASMA drugs imipramine, v amitriptyline, desipramine, nortriptyline, and sertraline in combination with UVB-, PAF-or phorbol ester-mediated MVP release. This study suggests that FIASMA drugs can block MVP release in response to multiple skin stressors on human HaCaT keratinocyte cells, as well as human and porcine skin explants.

Department or Program

Department of Pharmacology and Toxicology

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