Dual role of interferon-gamma signalling pathway in sensitivity of pancreatic beta cells to immune destruction.

摘要: Aims/hypothesis. Disruption of the interferon-gamma (IFN-γ) signalling pathway at level interferon regulatory factor-1 (IRF-1) protects islets against cytokine-induced nitric oxide production and cell death in vitro. The aim this study was to investigate effects a global disruption IFN-γ signalling, or selective IRF-1, on beta-cell sensitivity vivo immune destruction. Methods. In first set experiments, receptor knockout mice (IFN-γR-/-) (IRF-1-/-) were rendered diabetic by injections 50 mg streptozotocin i. p. 5 consecutive days (MLDSTZ). Results. Whereas no difference MLDSTZ-induced diabetes could be observed between IFN-γR-/- their 129/Sv/Ev controls (50 % vs 55 %, NS), there an increased incidence IRF-1-/- (100 67 C57Bl/6 mice, p < 0.05). A similar destruction when these used as allografts. Islet graft survival rate islets, transplanted alloxan-diabetic BALB/c recipients, comparable (12.0 ± 1.9 12.9 2.3 days, NS). Allograft rejection, however, recipients occurred more rapidly than following transplantation (9.1 2.0 13.1 1.5 0.003). Conclusions/interpretation. These data indicate that signal transduction is not essential for vivo. Moreover, IRF-1 gene pancreatic increases susceptibility killing, suggesting might necessary expression putative “defence and/or repair” genes. [Diabetologia (2001) 44: 567–574]