首页> 外文期刊>Hormone and Metabolic Research >Metabolic Endotoxemia-Activated Macrophages Promote Pancreatic Cell Death via IFN-Xaf1 Pathway
【24h】

Metabolic Endotoxemia-Activated Macrophages Promote Pancreatic Cell Death via IFN-Xaf1 Pathway

机译:代谢内毒素激活的巨噬细胞通过IFN-XAF1途径促进胰腺细胞死亡

获取原文
获取原文并翻译 | 示例
获取外文期刊封面目录资料

摘要

Metabolic endotoxemia has been implicated in the pathogenesis of type 2 diabetes. In addition to adipose tissue inflammation, inflammatory cell infiltration is also observed in islets, although its effect on islets is largely unknown. We hypothesized that macrophage infiltration into islets leads to impairment of or cell function, which ultimately act to exacerbate the pathophysiology of diabetes. Gene expression in a murine cell line, TC1, and cell line, TC6, was investigated by DNA microarray after co-culturing the cells with a murine macrophage cell line, RAW 264.7, in the presence or absence of bacterial endotoxin. Among the genes showing highly upregulated expression, genes specifically upregulated only in cells were evaluated to determine the roles of the gene products on the cellular function of cells. In both and cells, expression of type I interferon-responsive genes was highly upregulated upon endotoxin stimulation. Among these genes, expression of the X-linked inhibitor of apoptosis (Xiap)-associated factor 1 (Xaf1) gene, which is associated with the induction of apoptosis, was specifically enhanced in cells by endotoxin stimulation. This upregulation appeared to be mediated by macrophage-derived interferon (IFN), as endotoxin-stimulated macrophages produced higher amounts of IFN, and exogenous addition of IFN into TC6 cultures resulted in increased Xaf1 protein production and cleaved caspase 3, which accelerated -cell apoptosis. Macrophages activated by metabolic endotoxemia infiltrated into islets and produced IFN, which induced -cell apoptosis by increasing the expression of Xaf1.
机译:代谢内毒性血症已涉及2型糖尿病的发病机制。除了脂肪组织炎症之外,胰岛也观察到炎症细胞浸润,尽管其对胰岛的影响主要是未知的。我们假设巨噬细胞浸润进入胰岛导致损害或细胞功能损害,这最终会加剧糖尿病的病理生理学。通过在将细胞与细菌内毒素的存在或不存在的情况下,通过DNA微阵列研究了鼠细胞系,TC1和细胞系TC6,TC1和细胞系TC6的基因表达TC6。在显示高度上调表达的基因中,评价仅在细胞中特别上调的基因以确定基因产物对细胞细胞功能的作用。在两种和细胞中,在内毒素刺激后高度上调I型干扰素响应基因的表达。在这些基因中,通过内毒素刺激在细胞中特别提高了与凋亡的诱导相关的凋亡(XIAP) - 分配因子1(XAF1)基因的表达。这种上调似乎由巨噬细胞衍生的干扰素(IFN)介导,因为内毒素刺激的巨噬细胞产生了较高量的IFN,并且IFN进入TC6培养物的外源添加导致XAF1蛋白质产生增加和切割的Caspase 3,其加速 - 细胞凋亡。通过代谢内毒素浸润的巨噬细胞激活到胰岛中并产生IFN,通过增加XAF1的表达诱导-Cell凋亡。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号