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NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration
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-associate...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730317/ https://www.ncbi.nlm.nih.gov/pubmed/26760997 http://dx.doi.org/10.3390/ijms17010073 |
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author | Wang, Yujuan Hanus, Jakub W. Abu-Asab, Mones S. Shen, Defen Ogilvy, Alexander Ou, Jingxing Chu, Xi K. Shi, Guangpu Li, Wei Wang, Shusheng Chan, Chi-Chao |
author_facet | Wang, Yujuan Hanus, Jakub W. Abu-Asab, Mones S. Shen, Defen Ogilvy, Alexander Ou, Jingxing Chu, Xi K. Shi, Guangpu Li, Wei Wang, Shusheng Chan, Chi-Chao |
author_sort | Wang, Yujuan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4730317 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-47303172016-02-11 NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration Wang, Yujuan Hanus, Jakub W. Abu-Asab, Mones S. Shen, Defen Ogilvy, Alexander Ou, Jingxing Chu, Xi K. Shi, Guangpu Li, Wei Wang, Shusheng Chan, Chi-Chao Int J Mol Sci Article 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. MDPI 2016-01-08 /pmc/articles/PMC4730317/ /pubmed/26760997 http://dx.doi.org/10.3390/ijms17010073 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons by Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wang, Yujuan Hanus, Jakub W. Abu-Asab, Mones S. Shen, Defen Ogilvy, Alexander Ou, Jingxing Chu, Xi K. Shi, Guangpu Li, Wei Wang, Shusheng Chan, Chi-Chao NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration |
title | NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration |
title_full | NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration |
title_fullStr | NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration |
title_full_unstemmed | NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration |
title_short | NLRP3 Upregulation in Retinal Pigment Epithelium in Age-Related Macular Degeneration |
title_sort | nlrp3 upregulation in retinal pigment epithelium in age-related macular degeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4730317/ https://www.ncbi.nlm.nih.gov/pubmed/26760997 http://dx.doi.org/10.3390/ijms17010073 |
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