NF-κB is weakly activated in the NOD mouse model of type 1 diabetes.

Irvin AE, Jhala G, Zhao Y, Blackwell TS, Krishnamurthy B, Thomas HE, Kay TWH
Sci Rep. 2018 8 (1): 4217

PMID: 29523846 · PMCID: PMC5844878 · DOI:10.1038/s41598-018-22738-3

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-κB) regulates innate and adaptive immune responses. Using gene targeting and in vitro analysis of pancreatic islets and immune cells, NF-κB 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-κB 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-κB. However, activated NF-κB 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-κB 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.

MeSH Terms (9)

Animals Dendritic Cells Diabetes Mellitus, Type 1 Disease Models, Animal Macrophages Mice Mice, Inbred NOD NF-kappa B Transcription, Genetic

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