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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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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. |
format | Online Article Text |
id | pubmed-9233592 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
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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