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Published on: May 6, 2013
Knockdown of IFNAR2 reduces the inflammatory response in mouse model of type 1 diabetes
Wei Sun1, Jing Liu2, Renhao Zhao3
1Department of Clinical Laboratory, The Affiliated Lianyungang Hospital of Xuzhou Medical University, The First People's Hospital of Lianyungang, The Affiliated Hospital of Kangda College of Nanjing Medical University, Lianyungang, JiangSu, 222061, China.
Background:
and Purpose: To investigate the biological role of interferon α/β receptor 2 (IFNAR2) in type 1 diabetes (T1D).
Methods:
First, IFNAR2 mRNA and protein expression levels in serum of T1D patients and healthy controls were detected by RT-qPCR and Western blot. For experimental studies, 80 male C57BL/6 mice were randomly divided into 4 groups with 20 mice in each group: the control group, the T1D group, the T1D + ad-con group and the T1D + ad-si-IFNAR2 group. The T1D mouse model was generated by multiple intraperitoneal injections of small doses of streptozotocin (STZ). Body weight and blood glucose levels were measured weekly until 6 weeks. After 6 weeks, all mice were sacrificed and the levels of insulin (Ins), tumor necrosis factor α (TNF-α), interleukin 4 (IL-4), IL-6, and type I interferon γ (IFN-γ), IFNAR2 protein expression, the number of dendritic cells (DCs), and changes in islet β cells were assessed.
Results:
IFNAR2 mRNA and protein expression levels in serum of T1D patients were significantly higher than those in healthy controls (P < 0.05). Furthermore, IFNAR2 protein expression, number of DCs, and IFNAR2 mRNA, blood glucose, TNF-α, and IFN-γ levels were significantly upregulated in T1D mice compared with the control group (P < 0.05), while weight, and Ins, IL-6, and IL-4 levels were decreased (P < 0.05). However, knockdown of IFNAR2 reversed these trends. There was no significant difference in markers between the T1D + ad-con group and the T1D group (P > 0.05).
Conclusions:
Knockdown of IFNAR2 reduced the inflammatory response and improved islet function of T1D mice.
Insights
Interferon alpha/beta receptor 2 (IFNAR2) is elevated in type 1 diabetes (T1D). Reducing IFNAR2 in T1D mice lessened inflammation and improved pancreatic islet function.
Area of Science:
- Immunology
- Endocrinology
- Diabetes Research
Background:
- Type 1 diabetes (T1D) is an autoimmune disease characterized by pancreatic beta cell destruction.
- The role of interferon signaling pathways in T1D pathogenesis is an area of active investigation.
- Interferon alpha/beta receptor 2 (IFNAR2) is a key component of the type I interferon signaling pathway.
Purpose of the Study:
- To investigate the biological role and expression of interferon alpha/beta receptor 2 (IFNAR2) in type 1 diabetes (T1D).
- To determine the therapeutic potential of targeting IFNAR2 in a mouse model of T1D.
Main Methods:
- IFNAR2 mRNA and protein levels were measured in serum from T1D patients and healthy controls.
- A type 1 diabetes mouse model was induced using streptozotocin (STZ).
- IFNAR2 was knocked down in T1D mice using adeno-associated virus (AAV) vectors carrying short interfering RNA (siRNA).
- Measurements included body weight, blood glucose, insulin levels, inflammatory cytokines (TNF-α, IL-4, IL-6, IFN-γ), and pancreatic islet morphology.
Main Results:
- Serum IFNAR2 mRNA and protein levels were significantly higher in T1D patients compared to healthy controls.
- T1D mice exhibited upregulated IFNAR2 expression, increased blood glucose, elevated inflammatory markers (TNF-α, IFN-γ), and a higher number of dendritic cells (DCs).
- Conversely, T1D mice showed decreased body weight, insulin levels, and IL-4/IL-6, which were reversed upon IFNAR2 knockdown.
Conclusions:
- Elevated IFNAR2 expression is associated with type 1 diabetes.
- Targeting and reducing IFNAR2 in T1D mice ameliorates the inflammatory response.
- IFNAR2 knockdown demonstrates potential therapeutic benefits for improving pancreatic islet function in T1D.
