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Aβ1–40 Oligomers Trigger Neutrophil Extracellular Trap Formation through TLR4- and NADPH Oxidase-Dependent Pathways in Age-Related Macular Degeneration

Neutrophils participate in the advancement of the human innate immune system and respond to perceived endogenous and exogenous threats. As a response mechanism, neutrophil extracellular traps (NETs) form near pathogens and surrounding tissues during an immune response. Drusen is an important marker...

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Autores principales: Chen, Jinquan, Zhao, Long, Ding, Xuanheng, Wen, Yan, Wang, Lingda, Shu, Qinxin, Xie, Wenxi, Liu, Yanyao, Peng, H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233592/
https://www.ncbi.nlm.nih.gov/pubmed/35761872
http://dx.doi.org/10.1155/2022/6489923
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author Chen, Jinquan
Zhao, Long
Ding, Xuanheng
Wen, Yan
Wang, Lingda
Shu, Qinxin
Xie, Wenxi
Liu, Yanyao
Peng, H.
author_facet Chen, Jinquan
Zhao, Long
Ding, Xuanheng
Wen, Yan
Wang, Lingda
Shu, Qinxin
Xie, Wenxi
Liu, Yanyao
Peng, H.
author_sort Chen, Jinquan
collection PubMed
description Neutrophils participate in the advancement of the human innate immune system and respond to perceived endogenous and exogenous threats. As a response mechanism, neutrophil extracellular traps (NETs) form near pathogens and surrounding tissues during an immune response. Drusen is an important marker of Age-Related Macular Degeneration (AMD) and plays an important role in the course of AMD. Aβ1-40 is the main component of drusen. However, the relationship between NETs and AMD or Aβ1-40 is unclear. Here, we found elevated levels of NETs in the serum of AMD patients and elevated levels in the serum of mouse models. We also observed the accumulation of neutrophils in the mouse retina. In addition, the production of NETs was inhibited by PAD4 inhibitors, which can alleviate chronic inflammation. Moreover, we confirmed that Aβ1-40 can induce NETs formation via the Toll-like receptor 4 (TLR4) and neutrophil NADPH oxidase (NOX) pathways. Our study confirmed that the formation of NETs is induced by Aβ1–40, and the results suggest that NETs may play a vital role in AMD pathogenesis.
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spelling pubmed-92335922022-06-26 Aβ1–40 Oligomers Trigger Neutrophil Extracellular Trap Formation through TLR4- and NADPH Oxidase-Dependent Pathways in Age-Related Macular Degeneration Chen, Jinquan Zhao, Long Ding, Xuanheng Wen, Yan Wang, Lingda Shu, Qinxin Xie, Wenxi Liu, Yanyao Peng, H. Oxid Med Cell Longev Research Article Neutrophils participate in the advancement of the human innate immune system and respond to perceived endogenous and exogenous threats. As a response mechanism, neutrophil extracellular traps (NETs) form near pathogens and surrounding tissues during an immune response. Drusen is an important marker of Age-Related Macular Degeneration (AMD) and plays an important role in the course of AMD. Aβ1-40 is the main component of drusen. However, the relationship between NETs and AMD or Aβ1-40 is unclear. Here, we found elevated levels of NETs in the serum of AMD patients and elevated levels in the serum of mouse models. We also observed the accumulation of neutrophils in the mouse retina. In addition, the production of NETs was inhibited by PAD4 inhibitors, which can alleviate chronic inflammation. Moreover, we confirmed that Aβ1-40 can induce NETs formation via the Toll-like receptor 4 (TLR4) and neutrophil NADPH oxidase (NOX) pathways. Our study confirmed that the formation of NETs is induced by Aβ1–40, and the results suggest that NETs may play a vital role in AMD pathogenesis. Hindawi 2022-06-18 /pmc/articles/PMC9233592/ /pubmed/35761872 http://dx.doi.org/10.1155/2022/6489923 Text en Copyright © 2022 Jinquan Chen et al. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chen, Jinquan
Zhao, Long
Ding, Xuanheng
Wen, Yan
Wang, Lingda
Shu, Qinxin
Xie, Wenxi
Liu, Yanyao
Peng, H.
Aβ1–40 Oligomers Trigger Neutrophil Extracellular Trap Formation through TLR4- and NADPH Oxidase-Dependent Pathways in Age-Related Macular Degeneration
title Aβ1–40 Oligomers Trigger Neutrophil Extracellular Trap Formation through TLR4- and NADPH Oxidase-Dependent Pathways in Age-Related Macular Degeneration
title_full Aβ1–40 Oligomers Trigger Neutrophil Extracellular Trap Formation through TLR4- and NADPH Oxidase-Dependent Pathways in Age-Related Macular Degeneration
title_fullStr Aβ1–40 Oligomers Trigger Neutrophil Extracellular Trap Formation through TLR4- and NADPH Oxidase-Dependent Pathways in Age-Related Macular Degeneration
title_full_unstemmed Aβ1–40 Oligomers Trigger Neutrophil Extracellular Trap Formation through TLR4- and NADPH Oxidase-Dependent Pathways in Age-Related Macular Degeneration
title_short Aβ1–40 Oligomers Trigger Neutrophil Extracellular Trap Formation through TLR4- and NADPH Oxidase-Dependent Pathways in Age-Related Macular Degeneration
title_sort aβ1–40 oligomers trigger neutrophil extracellular trap formation through tlr4- and nadph oxidase-dependent pathways in age-related macular degeneration
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9233592/
https://www.ncbi.nlm.nih.gov/pubmed/35761872
http://dx.doi.org/10.1155/2022/6489923
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