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Recent progress in research on beta-cell apoptosis by cytokines
Kyoung-Ah Kim1,Myung-Shik Lee1
1
Department of Medicine, Dongguk University International Hospital,Dongguk University School of Medicine, Goyang, Korea
DOI: 10.2741/3271 Volume 14 Issue 2, pp.657-664
Published: 01 January 2009
(This article belongs to the Special Issue Recent progress in signal transduction of islet beta cells)
Abstract

Pancreatic beta-cell apoptosis plays a critical role in the pathogenesis of type 1 diabetes mellitus. As death effector molecules, perforin, Fas ligand, tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1, interferon (IFN)-gamma, and nitric oxide have been claimed. Recently, combinations or synergisms between IFN-gamma and TNF-alpha or IL-1beta are being revisited as the death effectors, and signal transduction of such synergisms has been explored to find molecular mechanism of beta -cell death. Among the regulators of apoptosis, nuclear factor-kappaB (NF-kappaB) has emerged as a master switch of cytokine-induced beta -cell dysfunction and death. By employing TNF-alpha / IFN-gamma synergism model which causes beta -cell apoptosis, we found that the antiapoptotic X-linked inhibitor of apoptosis (XIAP) molecule is upregulated by NF-kappaB in response to TNF-alpha and XIAP induction was inhibited by IFN-gamma-induced signal transducer and activator of transcription-1 (STAT1) activation, which explains the death of beta -cells by TNF-alpha /IFN-gamma synergism.

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Kyoung-Ah Kim, Myung-Shik Lee. Recent progress in research on beta-cell apoptosis by cytokines. Frontiers in Bioscience-Landmark. 2009. 14(2); 657-664.