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Recombinant adenoviral expression of IL-10 protects beta cell from impairment induced by pro-inflammatory cytokine

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Abstract

Interleukin-10 (IL-10) is a pleiotropic immunosuppressive and immunostimulatory cytokine. In autoimmune diabetes of the nonobese diabetic (NOD) mouse, IL-10 has exhibited paradoxical effects. Systemic IL-10 expression prevented or delayed diabetes onset in NOD mice while local expression of IL-10 did not. As antigen-presenting cells (APCs) play a central role in the generation of primary T cell responses, the direct role of this gene in pancreatic beta (β) cell is not clear. The effects of IL-10 on the protection of β cells in vitro were examined. In the present study, we examined the effects of adenovirus vector-mediated murine IL-10 (mIL-10) gene transfer to islet cell line RINm5F cells in vitro and to explore if IL-10 overexpression may prevent cytokine-mediated cytotoxicity. We had established the recombinant adenovirus vector containing mIL-10 genes (Ad-mIL-10) successfully. After infection of Ad-mIL-10, both mRNA and protein were expressed in RINm5F cells. Moreover, RINm5F cells secreted IL-10 protein into culture medium. Ad-mIL-10 prevented IL-1β-mediated nitric oxide production from β cells in vitro as well as the suppression of β cells function as determined by glucose-stimulated insulin production. Furthermore, Ad-mIL-10 gene transfer led to a profound reduction of Fas-expressing β cells and caspase-3 activity which were induced by IL-1β and the apoptotic rates of Ad-mIL-10 group were decreased. These findings show that IL-10 gene transfer to β cells may be beneficial in maintaining cells function, protecting islet cells from apoptosis—mediated by factors, which showed the potential therapy for type 1 diabetes mellitus.

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Acknowledgments

This project was supported by a grant from the Natural Science Foundation of Shandong province (grant no: Y2008C50). We appreciated Prof. Bing Luo and Dr. Zhi-hong Chen for their excellent technique assistance.

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Authors and Affiliations

  1. Department of Pediatrics, Affiliated Hospital of Qingdao Medical College, Qingdao University, Qingdao, 266003, China

    Ai-Jing Xu, Fei Tian, Li-Hua Yan & Tang Li

  2. State Key Laboratory of Oncology in Southern China, Cancer Center, Sun Yat-sen University, Guangzhou, 510060, China

    Wei Zhu

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  1. Ai-Jing Xu
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Correspondence to Tang Li.

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Xu, AJ., Zhu, W., Tian, F. et al. Recombinant adenoviral expression of IL-10 protects beta cell from impairment induced by pro-inflammatory cytokine. Mol Cell Biochem 344, 163–171 (2010). https://doi.org/10.1007/s11010-010-0539-x

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  • DOI: https://doi.org/10.1007/s11010-010-0539-x

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