Interferon-gamma-induced regulation of the pancreatic derived cytokine FAM3B in islets and insulin-secreting betaTC3 cells

Mol Cell Endocrinol. 2005 Aug 30;240(1-2):74-81. doi: 10.1016/j.mce.2005.05.010.

Abstract

The pancreatic-derived factor (PANDER, FAM3B) is a novel protein that is beta-cell specific and induces beta-cell death. PANDER is localized to insulin-containing granules-based on confocal microscopy and immunogold electron microscopy. PANDER protein was detected in the conditioned medium of betaTC3 cells. Using real-time reverse transcription-polymerase chain reaction, treatment of betaTC3 cells with IL-1beta + TNFalpha + IFNgamma induced a significant seven-fold increase in PANDER mRNA expression (n = 3; p < 0.01 at 24 h, p < 0.05 at 48 h), while IFNgamma alone caused a 3.2-fold increase (n = 3; p < 0.01 at 24 h) compared to unstimulated and time-matched vehicle controls. IL-1beta or TNFalpha alone had no effect. Under those conditions, a similar up-regulation was also observed in mouse islet cells, with increases in PANDER mRNA of 5.9-fold and 5.0-fold after treatment with IL-1beta + TNFalpha + IFNgamma or IFNgamma alone. Because PANDER mRNA expression is up-regulated by IFNgamma, a cytokine implicated in the pathogenesis of type 1 diabetes, PANDER may contribute to the pathogenesis of beta-cell death.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Cell Line
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Cytokines / pharmacology
  • Cytokines / physiology
  • Interferon-gamma / pharmacology
  • Interferon-gamma / physiology*
  • Islets of Langerhans / chemistry
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / metabolism*
  • Mice
  • Pancreas / cytology
  • RNA, Messenger / metabolism
  • Rats
  • Up-Regulation

Substances

  • Cytokines
  • PANDER protein, mouse
  • RNA, Messenger
  • Interferon-gamma