期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 344, 期 1-2, 页码 163-171出版社
SPRINGER
DOI: 10.1007/s11010-010-0539-x
关键词
Adenovirus; Interleukin-10; Insulin-secreting cells; Apoptosis
类别
资金
- Natural Science Foundation of Shandong province [Y2008C50]
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 (beta) cell is not clear. The effects of IL-10 on the protection of beta 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-1 beta-mediated nitric oxide production from beta cells in vitro as well as the suppression of beta cells function as determined by glucose-stimulated insulin production. Furthermore, Ad-mIL-10 gene transfer led to a profound reduction of Fas-expressing beta cells and caspase-3 activity which were induced by IL-1 beta and the apoptotic rates of Ad-mIL-10 group were decreased. These findings show that IL-10 gene transfer to beta 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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