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

Irina I. Zaitseva, Monica Hultcrantz, Vladimir Sharoyko, Malin Flodström-Tullberg, Sergei V. Zaitsev, Per Olof Berggren

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)3787-3795
Number of pages9
JournalCellular and Molecular Life Sciences
Volume66
Issue number23
DOIs
StatePublished - Jan 1 2009

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Keywords

  • Apoptosis
  • Caspase
  • Cytokine
  • Interferon-gamma
  • Islets of Langerhans
  • Pancreatic beta-cell

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Molecular Medicine
  • Pharmacology
  • Cellular and Molecular Neuroscience

Cite this

Zaitseva, I. I., Hultcrantz, M., Sharoyko, V., Flodström-Tullberg, M., Zaitsev, S. V., & Berggren, P. O. (2009). Suppressor of cytokine signaling-1 inhibits caspase activation and protects from cytokine-induced beta cell death. Cellular and Molecular Life Sciences, 66(23), 3787-3795. https://doi.org/10.1007/s00018-009-0151-y