NF-κB is weakly activated in the NOD mouse model of type 1 diabetes
Autor: | Helen E. Thomas, Allison E. Irvin, Yuxing Zhao, Timothy S. Blackwell, Gaurang Jhala, Thomas W.H. Kay, Balasubramanian Krishnamurthy |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Transcription Genetic T cell lcsh:Medicine Nod Article 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Immune system Mice Inbred NOD medicine Animals lcsh:Science NOD mice Type 1 diabetes Multidisciplinary Pancreatic islets Macrophages lcsh:R NF-kappa B NF-κB Dendritic Cells medicine.disease NFKB1 3. Good health Disease Models Animal 030104 developmental biology medicine.anatomical_structure Diabetes Mellitus Type 1 chemistry 030220 oncology & carcinogenesis Cancer research lcsh:Q |
Zdroj: | Scientific Reports Scientific Reports, Vol 8, Iss 1, Pp 1-7 (2018) |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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