IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo

IL-6 protects pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment in vitro and in vivo
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DOI:
10.1016/j.trim.2004.04.001
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发表时间:
2004-06-01
影响因子:
1.5
通讯作者:
Park, CG
Park, CG
中科院分区:
医学4区
文献类型:
--
作者:
Choi, SE;Choi, KM;Park, CG

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保护胰岛β细胞免受促炎细胞因子诱导的细胞死亡和功能损伤是开发I型糖尿病治疗干预(包括胰岛移植)的关键问题。检测了IL-6在体外和体内对β细胞的保护作用。当与IL-6预孵育时,新鲜分离的胰岛或MIN 6 β细胞显示出显著更高的存活率,所述存活率通过PI染色的细胞的MTT测定和FACS分析测量,针对由IL-1 β、TNF-α和IFN-γ递送的促凋亡信号传导。在葡萄糖和KCl刺激的静态培养中,胰岛素分泌功能也受到显著保护。在小鼠模型中使用边缘质量同基因胰岛移植的体内评估显示IL-6在50天内赋予显著更好的血糖控制和移植物存活率。总之,IL-6在体外和体内保护胰岛或β细胞免受炎性细胞因子诱导的细胞死亡和功能损伤。这种策略可以在临床上用于维持功能性胰岛质量。(C)2004 Elsevier B. V.保留所有权利。
Protection of pancreatic islet beta cells from pro-inflammatory cytokines-induced cell death and functional impairment is a key issue in developing therapeutic interventions of type I diabetes mellitus including islet transplantation. The effects of IL-6 on the protection of beta cells in vitro and in vivo were examined. Freshly isolated islets or MIN6 beta cells, when pre-incubated with IL-6, showed significantly higher viabilities measured by MTT assay and FACS analysis of PI stained cells against pro-apoptotic signaling delivered by IL-1beta, TNF-alpha and IFN-gamma. Insulin secretory function was also significantly protected in static culture with glucose and KCl stimulation. In vivo assessment using marginal mass syngeneic islet transplantation in mouse model revealed IL-6 conferred significantly better blood glucose control and graft survival rate over 50 days. Conclusively, IL-6 protects pancreatic islets or beta-cells from inflammatory cytokines-induced cell death and functional impairment both in vitro and in vivo. This strategy could be exploited in the clinical setting to maintain functional islet mass. (C) 2004 Elsevier B.V. All rights reserved.