1. Suppressor of cytokine signaling-1 inhibits caspase activation and protects from cytokine-induced beta cell death.
- Author
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Zaitseva, Irina I., Hultcrantz, Monica, Sharoyko, Vladimir, Flodström-Tullberg, Malin, Zaitsev, Sergei V., and Berggren, Per-Olof
- Subjects
PANCREATIC beta cells ,CYTOKINES ,INTERLEUKINS ,DIABETES prevention ,LABORATORY rats ,INTERFERONS - Abstract
Pancreatic beta cell damage caused by pro-inflammatory cytokines interleukin-1β (IL-1β), interferon-γ (IFNγ) and tumor necrosis factor-α (TNFα) is a key event in the pathogenesis of type 1 diabetes. The suppressor of cytokine signaling-1 (SOCS-1) blocks IFNγ-induced signaling and prevents diabetes in the non-obese diabetic mouse. Here, we investigated if SOCS-1 overexpression in primary beta cells provides protection from cytokine-induced islet cell dysfunction and death. We demonstrate that SOCS-1 does not prevent increase in NO production and decrease in glucose-stimulated insulin secretion in the presence of IL-1β, IFNγ, TNFα. However, it decreases the activation of caspase-3, -8 and -9, and thereby, promotes a robust protection from cytokine-induced beta cell death. Our data suggest that SOCS-1 overexpression may not be sufficient in preventing all the biological activities of IFNγ in beta cells. In summary, we show that interference with IFNγ signal transduction pathways by SOCS-1 inhibits cytokine-stimulated pancreatic beta cell death. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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