Recent progress in research on beta-cell apoptosis by cytokines

Front Biosci (Landmark Ed). 2009 Jan 1;14:657-64. doi: 10.2741/3271.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cytokines / physiology*
  • Diabetes Mellitus, Type 1 / physiopathology
  • Islets of Langerhans / cytology*
  • Mice
  • NF-kappa B / physiology
  • STAT1 Transcription Factor / physiology
  • Up-Regulation
  • X-Linked Inhibitor of Apoptosis Protein / physiology

Substances

  • Cytokines
  • NF-kappa B
  • STAT1 Transcription Factor
  • X-Linked Inhibitor of Apoptosis Protein