Interferon-gamma-induced regulation of the pancreatic derived cytokine FAM3B in islets and insulin-secreting betaTC3 cells.
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.
Xu
Weizhen
W
Department of Pathology and Laboratory Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 19104, USA.
Gao
Zhiyong
Z
Wu
Jianmei
J
Wolf
Bryan A
BA
D000818:Animals; D002460:Cell Line; D016207:Cytokines / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology / Q000502:physiology; D007371:Interferon-gamma / Q000494:pharmacology / Q000502:physiology*; D007515:Islets of Langerhans / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010179:Pancreas / Q000166:cytology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D015854:Up-Regulation
D016207:Cytokines; C504749:PANDER protein, mouse; D012333:RNA, Messenger; D007371:Interferon-gamma