...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>International Journal of Molecular Sciences >NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration
【24h】

NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration

机译：年龄相关性黄斑变性中视网膜色素上皮中的NLRP3上调。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Inflammation and oxidative stress are involved in age-related macular degeneration (AMD) and possibly associated with an activation of neuronal apoptosis inhibitor protein/class II transcription activator of the Major Histocompatibility Complex (MHC)/heterokaryon incompatibility/telomerase-associated protein 1, leucine-rich repeat or nucleotide-binding domain, leucine-rich repeat-containing family, and pyrin domain-containing 3 (NLRP3) inflammasome. In the present study, we used a translational approach to address this hypothesis. In patients with AMD, we observed increased mRNA levels of NLRP3, pro-interleukin-1 beta (IL-1β) and pro-IL-18 in AMD lesions of the retinal pigment epithelium (RPE) and photoreceptor. In vitro, a similar increase was evoked by oxidative stress or lipopolysaccharide (LPS) stimulation in the adult retinal pigment epithelium (ARPE-19) cell line, and the increase was reduced in siRNA transfected cells to knockdown NLRP3. Ultrastructural studies of ARPE-19 cells showed a swelling of the cytoplasm, mitochondrial damage, and occurrence of autophagosome-like structures. NLRP3 positive dots were detected within autophagosome-like structures or in the extracellular space. Next, we used a mouse model of AMD, Ccl2/Cx3cr1 double knockout on rd8 background (DKO rd8) to ascertain the in vivo relevance. Ultrastructural studies of the RPE of these mice showed damaged mitochondria, autophagosome-like structures, and cytoplasmic vacuoles, which are reminiscent of the pathology seen in stressed ARPE-19 cells. The data suggest that the NLRP3 inflammasome may contribute in AMD pathogenesis.
机译：炎症和氧化应激与年龄相关性黄斑变性（AMD）有关，并可能与主要组织相容性复合体（MHC）/异核细胞不相容性/端粒酶相关蛋白1，亮氨酸的神经元凋亡抑制剂蛋白/ II类转录激活因子的激活有关。富集重复序列或核苷酸结合结构域，富亮氨酸包含重复序列家族和含吡喃结构域的3（NLRP3）炎性小体。在本研究中，我们使用了一种翻译方法来解决这个假设。在患有AMD的患者中，我们观察到视网膜色素上皮（RPE）和感光细胞的AMD病变中NLRP3，pro-interleukin-1 beta（IL-1β）和pro-IL-18 mRNA水平升高。在体外，成年视网膜色素上皮细胞（ARPE-19）细胞系中的氧化应激或脂多糖（LPS）刺激引起了类似的增加，而siRNA转染的细胞中的这种减少减少了NLRP3的表达。 ARPE-19细胞的超微结构研究显示细胞质肿胀，线粒体损伤和自噬样结构的出现。在自噬体样结构内或细胞外空间中检测到NLRP3阳性点。接下来，我们在rd8背景（DKO rd8）上使用了AMD小鼠模型Ccl2 / Cx3cr1双敲除来确定体内相关性。这些小鼠的RPE的超微结构研究显示线粒体受损，自噬体样结构和胞质液泡，这让人想起在压力ARPE-19细胞中看到的病理。数据表明NLRP3炎性小体可能与AMD的发病机理有关。

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