Interleukin-10 gene transfer into insulin-producing β cells protects against diabetes in non-obese diabetic mice

Xu,Aijing; Zhu,Wei; Li,Tang; Li,Xiuzhen; Cheng,Jing; Li,Cuiling; Yi,Peng; Liu,Li

doi:10.3892/mmr.2015.3809

Interleukin-10 gene transfer into insulin-producing β cells protects against diabetes in non-obese diabetic mice

Authors:
- Aijing Xu
- Wei Zhu
- Tang Li
- Xiuzhen Li
- Jing Cheng
- Cuiling Li
- Peng Yi
- Li Liu
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Affiliations: Department of Pediatric Endocrinology and Metabolism, Guangzhou Women and Children's Medical Center, Guangzhou Medical College, Guangzhou, Guangdong 510520, P.R. China, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Guangdong Medical College, Dongguan, Guangdong 523808, P.R. China, Department of Pediatrics, The Affiliated Hospital of Qingdao Medical College, Qingdao University, Qingdao, Shandong 266003, P.R. China
Published online on: May 21, 2015 https://doi.org/10.3892/mmr.2015.3809
Pages: 3881-3889

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Abstract

Type 1 diabetes is an autoimmune disorder, which occurs due to β cell damage. Interleukin (IL)-10, a pleotropic cytokine, has been reported to have anti‑inflammatory, immunosuppressive and immunostimulatory properties. Administration of IL‑10 is known to prevent autoimmune diabetes in non‑obese diabetic (NOD) mice. However, the mechanism of IL‑10‑induced protection in NOD mice requires further investigation. The aim of the present study was to evaluate the protective effect of transgenic IL‑10 expression in pancreatic β cells against autoimmune damage in NOD mice and to elucidate its mechanism of action. Female NOD mice (9 weeks old) were intraperitoneally injected with an adenovirus carrying either IL‑10 (Adv‑IL‑10) or green fluorescent protein (Adv‑GFP). Blood glucose was monitored weekly and the expression of IL‑10 was evaluated using reverse transcription quantitative polymerase chain reaction. IL‑10 and interferon (IFN)‑γ expression levels in serum and splenocytes were analyzed. CD4+CD25+FoxP3+ T regulatory (Treg) cells were determined by flow cytometry. Apoptosis of pancreatic β cells was determined using a terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick‑end labeling assay and expression levels of Fas and caspase‑3 were estimated by immunohistochemistry analysis. The results revealed that mice treated with IL‑10 showed less severe insulitis and a lower incidence of diabetes compared with the saline control and Adv‑GFP groups. In addition, compared with the control group, IFN‑γ levels were decreased in sera and splenocytes, while IL‑10 expression was increased in sera only. The number of CD4+CD25+FoxP3+ Treg cells was increased in IL‑10‑injected mice. Furthermore, the expression levels of Fas and caspase‑3 were decreased in IL‑10‑injected mice compared with that of GFP‑injected and control mice, which was concomitant with a reduction in β cell apoptosis. In conclusion, the present study demonstrated that IL‑10 gene transfer reduced the expression of the inflammatory cytokines, attenuated pancreatic insulitis and inhibited β cell apoptosis. This therefore indicated that IL-10 reduced the incidence of diabetes in female NOD mice.

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