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Browsing by Subject "T1D"

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  • Kilpeläinen, Niko (2014)
    Type 1 diabetes (T1D) is a chronic autoimmune disease in which insulin-producing beta-cells in pancreatic islets are destroyed by the body's own immune system. Patients with T1D require a life-long treatment with exogenous insulin. In Finland the incidence of T1D is the highest in the world. Interleukin-17 producing T helper cells (Th17 cells) have been linked to the disease pathogenesis in animal models of T1D. Increased activation of Th17-immunity, including elevated expression of IL-17 and interleukin-22 (IL-22) in the peripheral blood has been associated with human T1D. Additionally, IL-17 has been demonstrated to be harmful to mouse beta cells and human pancreatic islets. The publications reporting detrimental effects of IL-17 on mouse beta cells and human pancreatic islets lack the information regarding the role of IL-22 in the inflammatory conditions mediated by the pro-inflammatory cytokines IL-1b, IFN-? and IL-17. The aim of this study was to examine the effects of IL-17 and IL-22 on mouse beta cells and human pancreatic islets under the inflammatory conditions mediated by IL-1b and IFN-?. Cytokine-induced apoptosis of mouse beta cells was studied using MIN6 cells. Gene expression of anti-apoptosis, beta-cell function and IL-17-signaling related genes was studied from cytokine-stimulated MIN6 cells. Stress response and apoptosis related genes were studied from the human pancreatic islets. The proportion of apoptotic and necrotic cells of cytokine stimulated MIN6 cells was studied with fluorescence microscopy. Gene expression analyses were performed with quantitative reverse transcription qPCR (RT-qPCR). In this study IL-17 and IL-22 was demonstrated to modulate the outcome of IL-1b and IFN-? induced stress response in mouse beta-cells and human pancreatic islets as measured by the changes in the frequency of apoptotic cells and gene expression of stress, function and cytokine-signaling related genes.