Amyloid β induces NLRP3 inflammasome activation in retinal pigment epithelial cells via NADPH oxidase‐ and mitochondria‐dependent ROS production
Amyloid β induces NLRP3 inflammasome activation in retinal pigment epithelial cells via NADPH oxidase‐ and mitochondria‐dependent ROS production
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DOI：
10.1002/jbt.21887
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发表时间：
2017-06
影响因子：
3.6
通讯作者：
Ke Wang;Yong Yao;Xue Zhu;Kai Zhang;Fanfan Zhou;Ling Zhu
中科院分区：
文献类型：
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作者：
Ke Wang;Yong Yao;Xue Zhu;Kai Zhang;Fanfan Zhou;Ling Zhu
β淀粉样蛋白（Aβ）诱导的慢性炎症被认为是早期年龄相关性黄斑变性（AMD）的关键致病过程。Aβ激活的含核甘酸寡聚化结构域（NOD）样受体家族3（NLRP 3）炎性小体激活是AMD发病时视网膜色素上皮（RPE）功能障碍的原因，但详细的分子机制尚不清楚。在这项研究中，我们研究了NADPH氧化酶和线粒体源性活性氧（ROS）在Aβ1-40诱导LPS致敏的ARPE-19细胞中NLRP 3炎性小体活化过程中的参与。结果显示，Aβ1-40可诱导LPS致敏的ARPE-19细胞产生过量的ROS、MAPK/NF-κB信号通路激活以及随后的NLRP 3炎性小体激活。此外，Aβ1-40对NLRP 3炎性小体激活的诱导作用是以依赖于NADPH氧化酶和线粒体源性ROS的方式介导的。我们的研究结果可能为Aβ参与早期AMD的分子机制提供新的见解。
Amyloid β (Aβ)‐induced chronic inflammation is believed to be a key pathogenic process in early‐stage age‐related macular degeneration (AMD). Nucleotide oligomerization domain (NOD)‐like receptor family, pyrin domain containing 3 (NLRP3) inflammasome activation triggered by Aβ is responsible for retinal pigment epithelium (RPE) dysfunction in the onset of AMD; however, the detailed molecular mechanism remains unclear. In this study, we investigated the involvement of NADPH oxidase‐ and mitochondria‐derived reactive oxygen species (ROS) in the process of Aβ1–40‐induced NLRP3 inflammasome activation in LPS‐primed ARPE‐19 cells. The results showed that Aβ1–40 could induce excessive ROS generation, MAPK/NF‐κB signaling activation and subsequently NLRP3 inflammasome activation in LPS‐primed ARPE‐19 cells. Furthermore, the inductive effect of Aβ1–40 on NLRP3 inflammasome activation was mediated in a manner dependent on NADPH oxidase‐ and mitochondria‐derived ROS. Our findings may provide a novel insight into the molecular mechanism by which Aβ contributes to the early‐stage AMD.