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• W2013285816 abstract "This study determined the role of the proinflammatory cytokines known to be elevated in the diabetic retina, namely IL-1beta, TNFalpha, and IL-6, in a high glucose-induced nuclear accumulation of GAPDH in retinal Müller cells, an event considered crucial for the induction of cell death.With use of the transformed rat Müller cell line (rMC-1) and isolated human Müller cells (HMCs), the authors examined the effect of high glucose (25 mM), IL-1beta, TNFalpha, IL-6, and high glucose (25 mM) plus inhibitors of the caspase-1/IL-1beta signaling pathway on GAPDH nuclear accumulation, which was evaluated by immunofluorescence analysis.High glucose induced IL-1beta, weak IL-6, and no TNFalpha production by rMC-1 and HMCs. IL-1beta (1-10 ng/mL) significantly increased GAPDH nuclear accumulation in Müller cells in a concentration-dependent manner within 24 hours. Further, high glucose-induced GAPDH nuclear accumulation in Müller cells was mediated by IL-1beta. Inhibition of the IL-1 receptor using an IL-1 receptor antagonist (IL-1ra; 50 ng/mL) or inhibition of IL-1beta production using a specific caspase-1 inhibitor (YVAD-fmk; 100 microM) significantly decreased high glucose-induced GAPDH nuclear accumulation. In contrast, IL-6 (2 ng/mL) had a strong protective effect attenuating high glucose and IL-1beta-induced GAPDH nuclear accumulation in Müller cells. TNFalpha (1-10 ng/mL) did not have any effect on GAPDH nuclear accumulation.These results revealed a novel mechanism for high glucose-induced GAPDH nuclear accumulation in Müller cells through production and autocrine stimulation by IL-1beta. The protective role of IL-6 in high glucose- and IL-1beta-induced toxicity indicates that changes in the balance of these cytokines might contribute to cellular damage mediated by elevated glucose levels." @default.
• W2013285816 created "2016-06-24" @default.
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• W2013285816 date "2009-04-01" @default.
• W2013285816 modified "2023-10-09" @default.
• W2013285816 title "Differential Regulation of High Glucose–Induced Glyceraldehyde-3-Phosphate Dehydrogenase Nuclear Accumulation in Müller Cells by IL-1β and IL-6" @default.
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• W2013285816 doi "https://doi.org/10.1167/iovs.08-2082" @default.
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