Cheryl Conley (Committee Member), Barbara Hull (Committee Chair), James Mcdougal (Committee Member)
Master of Science (MS)
Contact dermatitis is one of the most common occupational diseases. Absenteeism of the affected workers and associated health care costs makes this disease an economically important issue. Irritant contact dermatitis (ICD) is a common contact dermatitis observed among workers. As each category of irritants triggers the inflammatory process by different method, studying the mechanism of ICD is difficult. Information on the mechanism of action of an irritant is indispensable for the development of effective prophylactic and therapeutic measures. In this study, we have investigated the early changes in rat skin induced by jet fuel-8 (JP-8). Although previous studies have described the cytokines involved in the latter phase of the inflammatory process induced by JP-8, there is no information on the molecular mechanisms that leads to the downstream events. Gallucci et al., (2004) and Chatterjee et al., (2006) has shown that JP-8 induces elevated levels of interleukin-1 alpha (IL-1 alpha) in skin and cultured keratinocytes, respectively. The preformed and stored proinflammatory cytokine, IL-1 alpha that has autocrine and paracrine functions, appear to trigger the cascade of events that leads to the JP-8-induced contact dermatitis. We hypothesize that JP-8 induces increased levels of IL-1 alpha at early post-exposure time points. To test our hypothesis, we applied JP-8 in an occlusive patch for 1 h on the rat skin and measured IL-1 at 0, 1, 2, 3, 4, and 8 h post exposure. Neutrophils infiltrate the skin during the late phase of the inflammatory process; therefore we studied the neutrophil infiltration during the selected time points and measured the levels of CXCL2, the cytokine associated with the infiltration of neutrophils. Preformed and stored IL-1 might play an important role in the JP-8 induced gene expression in skin. We hypothesized that that blocking of IL-1 receptor will inhibit the JP-8 induced gene expression pattern. To test our hypothesis, we delivered IL-1 receptor antagonist into the skin before JP-8 treatment. We found that At 3 h post exposure, IL-1 alpha was reduced in JP-8 exposed skin and the selected time points were too early in the inflammatory cascade to reveal infiltration of neutrophils, although there was a slight increase in the level of CXCL2 at 2 h post exposure. Because IL-1 beta has similar biological effects, we measured this cytokine from the same samples used for IL-1 alpha quantification. IL-1 beta did not significantly change throughout the study. The decrease in the level of IL-1 alpha implies that JP-8 induces the release of the preformed IL-1 alpha. IL-1 receptor antagonist did not cause significant changes in the gene expression pattern. We conclude that the release of the preformed IL-1 alpha by JP-8 is one of the important events at the early time points of the JP-8-induced cascade of events.
Department or Program
Department of Biological Sciences
Year Degree Awarded
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