Suppressor of cytokine signaling-1 inhibits caspase activation and protects from cytokine-induced beta cell death

被引:0
作者
Irina I. Zaitseva
Monica Hultcrantz
Vladimir Sharoyko
Malin Flodström-Tullberg
Sergei V. Zaitsev
Per-Olof Berggren
机构
[1] Karolinska Institutet,The Rolf Luft Research Center for Diabetes and Endocrinology
[2] Karolinska University Hospital,Center for Infectious Medicine, Department of Medicine Huddinge
[3] L1,Belozersky Institute of Physico
[4] Karolinska Institutet,Chemical Biology
[5] Karolinska University Hospital Huddinge,undefined
[6] F59,undefined
[7] Lomonosov Moscow State University,undefined
来源
Cellular and Molecular Life Sciences | 2009年 / 66卷
关键词
Apoptosis; Islets of Langerhans; Pancreatic beta-cell; Cytokine; Caspase; Interferon-gamma;
D O I
暂无
中图分类号
学科分类号
摘要
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.
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页码:3787 / 3795
页数:8
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