Title: NF-kappa B is weakly activated in the NOD mouse model of type 1 diabetes
Authors: Irvin, AE
Jhala, G
Zhao, YX
Blackwell, TS
Krishnamurthy, B
Thomas, HE
Kay, TWH
Issue Year: 2018
Series Sci Rep:
Abstract Type 1 diabetes is an autoimmune disease characterised by selective destruction of pancreatic beta cells by the immune system. The transcription factor nuclear factor-kappa B (NF-kappa B) regulates innate and adaptive immune responses. Using gene targeting and in vitro analysis of pancreatic islets and immune cells, NF-kappa B activation has been implicated in type 1 diabetes development. Here we use a non-obese diabetic (NOD) mouse model that expresses a luciferase reporter of transcriptionally active NF-kappa B to determine its activation in vivo during development of diabetes. Increased luciferase activity was readily detected upon treatment with Toll-like receptor ligands in vitro and in vivo, indicating activation of NF-kappa B. However, activated NF-kappa B was detectable at low levels above background in unmanipulated NOD mice, but did not vary with age, despite the progression of inflammatory infiltration in islets over time. NF-kappa B was highly activated in an accelerated model of type 1 diabetes that requires CD4(+) T cells and inflammatory macrophages. These data shed light on the nature of the inflammatory response in the development of type 1 diabetes.
URI: https://publications.svi.edu.au/publications/4555
Other Identifiers 10.1038/s41598-018-22738-3
Publication type Article