| First Author | Mashima H | Year | 2011 |
| Journal | Gastroenterology | Volume | 141 |
| Issue | 3 | Pages | 1102-1113.e1-8 |
| PubMed ID | 21699790 | Mgi Jnum | J:309870 |
| Mgi Id | MGI:6708195 | Doi | 10.1053/j.gastro.2011.05.051 |
| Citation | Mashima H, et al. (2011) Interferon regulatory factor-2 regulates exocytosis mechanisms mediated by SNAREs in pancreatic acinar cells. Gastroenterology 141(3):1102-1113.e1-8 |
| abstractText | BACKGROUND & AIMS: Pancreatic acinar cells are used to study regulated exocytosis. We investigated the role of interferon regulatory factor-2 (IRF2) in exocytosis in pancreatic acinar cells. METHODS: Pancreas tissues from Irf2(+)/(+), Irf2(+)/(-)), and Irf2(-)/(-) mice were examined by microscopy, immunohistochemical, and immunoblot analyses; amylase secretion was quantified. We also compared salivary glands and pancreatic islets of Irf2(-)/(-) mice with those of Irf2(+)/(-) mice. To examine the effects of increased signaling by type I interferons, we studied pancreatic acini from Irf2(-)/(-)Ifnar1(-)/(-) mice. The effect of IRF2 on amylase secretion was studied using an acinar cell line and a retroviral system. We studied expression of IRF2 in wild-type mice with cerulein-induced pancreatitis and changes in pancreatic tissue of Irf2(-)/(-) mice, compared with those of Irf2(+)/(-) mice. RESULTS: Irf2(-)/(-) pancreas was white and opaque; numerous and wide-spread zymogen granules were observed throughout the cytoplasm, along with lack of fusion between zymogen granules and the apical membrane, lack of secretagogue-stimulated amylase secretion, and low serum levels of amylase and elastase-1, indicating altered regulation of exocytosis. The expression pattern of soluble N-ethylmaleimide-sensitive factor attachment protein receptors changed significantly, specifically in pancreatic acini, and was not rescued by disruption of type I interferon signaling. Down-regulation of IRF2 decreased amylase secretion in an acinar cell line. In mice with pancreatitis, levels of IRF2 were reduced. Irf2(-)/(-) acini were partially resistant to induction of pancreatitis. CONCLUSIONS: IRF2 regulates exocytosis in pancreatic acinar cells; defects in this process might be involved in the early phases of acute pancreatitis. |
