Amyloid β induces NLRP3 inflammasome activation in retinal pigment epithelial cells via NADPH oxidase‐ and mitochondria‐dependent ROS production |
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| Authors: | Ke Wang Yong Yao Xue Zhu Kai Zhang Fanfan Zhou Ling Zhu |
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| Institution: | 1. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi, Jiangsu Province, People's Republic of China;2. Department of Ophthalmology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu Province, People's Republic of China;3. Faculty of Pharmacy, University of Sydney, NSW, Australia;4. Save Sight Institute, University of Sydney, NSW, Australia |
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| Abstract: | 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. |
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| Keywords: | age‐related macular degeneration amyloid β NLRP3 inflammasome reactive oxygen species |
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