Interferon-γ-induced regulation of the pancreatic derived cytokine FAM3B in islets and insulin-secreting βTC3 cells

The pancreatic-derived factor (PANDER, FAM3B) is a novel protein that is β-cell specific and induces β-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 βTC3 cells. Using real-time reverse transcription-polymerase chain reaction, treatment of βTC3 cells with IL-1β + TNFα + IFNγ 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 IFNγ alone caused a 3.2-fold increase (n = 3; p < 0.01 at 24 h) compared to unstimulated and time-matched vehicle controls. IL-1β or TNFα 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-1β + TNFα + IFNγ or IFNγ alone. Because PANDER mRNA expression is up-regulated by IFNγ, a cytokine implicated in the pathogenesis of type 1 diabetes, PANDER may contribute to the pathogenesis of β-cell death.