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Date of Award
Anatomy and Cell Biology
Fu-shin X. Yu
The aim of this study was to elucidate the expression and functions of interleukin (IL)-24 and suppressor of cytokine signaling 3 (SOCS3), and their regulatory relationship in C57BL/6 mouse corneas in response to Pseudomonas aeruginosa (PA) infection. Among IL-20R cytokines, only IL-24 was induced at both mRNA and protein levels by the infection, and this upregulation was dampened by flagellin pretreatment. Time course studies revealed that IL-24 expression was markedly elevated, followed by a subsidence and second elevation, a pattern shared with SOCS3 but not IL-1β or IL-6. Silencing of IL-24 enhanced S100A8/A9 expression, and suppressed SOCS3, IL-1β, IL-1RN, and MMP13 expression during an early stage of infection. Downregulation of IL-24 signaling pathway significantly reduced the severity of keratitis, bacterial burden, and neutrophil infiltration; while recombinant IL-24 exacerbated PA keratitis. Furthermore, SOCS3 knockdown impaired the control of PA keratitis. In vitro, while IL-1β induced the expression of SOCS3, IL-24, IL-1β, and IL-6, IL-24 only elicited robust expression of SOCS3 in primarily cultured human corneal epithelial cells. In conclusion, IL-24 promotes PA keratitis by inducing SOCS3 expression, resulting in the suppression of the necessary inflammatory response at an early stage of infection, and in the increased severity of PA keratitis.
Xu, Bing, "Expression And Functions Of Il-24 And Socs3 In Pseudomonas Aeruginosa Keratitis In A C57bl/6 Mouse Model" (2016). Wayne State University Dissertations. 1607.