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Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells
Age-related macular degeneration (AMD) is a retinal disease leading to impaired vision. Cigarette smoke increases the risk for developing AMD by causing increased reactive oxygen species (ROS) production and damage in the retinal pigment epithelium (RPE). We have previously shown that the cigarette...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229790/ https://www.ncbi.nlm.nih.gov/pubmed/34204067 http://dx.doi.org/10.3390/cells10061405 |
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author | Bhattarai, Niina Korhonen, Eveliina Mysore, Yashavanthi Kaarniranta, Kai Kauppinen, Anu |
author_facet | Bhattarai, Niina Korhonen, Eveliina Mysore, Yashavanthi Kaarniranta, Kai Kauppinen, Anu |
author_sort | Bhattarai, Niina |
collection | PubMed |
description | Age-related macular degeneration (AMD) is a retinal disease leading to impaired vision. Cigarette smoke increases the risk for developing AMD by causing increased reactive oxygen species (ROS) production and damage in the retinal pigment epithelium (RPE). We have previously shown that the cigarette tar component hydroquinone causes oxidative stress in human RPE cells. In the present study, we investigated the propensity of hydroquinone to induce the secretion of interleukin (IL)-1β and IL-18. The activation of these cytokines is usually regulated by the Nucleotide-binding domain, Leucine-rich repeat, and Pyrin domain 3 (NLRP3) inflammasome. ARPE-19 cells were exposed to hydroquinone, and cell viability was monitored using the lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt (MTT) assays. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of proinflammatory cytokines IL-1β and IL-18 as well as NLRP3, caspase-1, and poly (ADP-ribose) polymerase (PARP). Hydroquinone did not change IL-1β release but significantly increased the secretion of IL-18. Cytoplasmic NLRP3 levels increased after the hydroquinone treatment of IL-1α-primed RPE cells, but IL-18 was equally released from primed and nonprimed cells. Hydroquinone reduced the intracellular levels of PARP, which were restored by treatment with the ROS scavenger N-acetyl-cysteine (NAC). NAC concurrently reduced the NLRP3 levels but had no effect on IL-18 release. In contrast, the NADPH oxidase inhibitor ammonium pyrrolidinedithiocarbamate (APDC) reduced the release of IL-18 but had no effect on the NLRP3 levels. Collectively, hydroquinone caused DNA damage seen as reduced intracellular PARP levels and induced NLRP3-independent IL-18 secretion in human RPE cells. |
format | Online Article Text |
id | pubmed-8229790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-82297902021-06-26 Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells Bhattarai, Niina Korhonen, Eveliina Mysore, Yashavanthi Kaarniranta, Kai Kauppinen, Anu Cells Article Age-related macular degeneration (AMD) is a retinal disease leading to impaired vision. Cigarette smoke increases the risk for developing AMD by causing increased reactive oxygen species (ROS) production and damage in the retinal pigment epithelium (RPE). We have previously shown that the cigarette tar component hydroquinone causes oxidative stress in human RPE cells. In the present study, we investigated the propensity of hydroquinone to induce the secretion of interleukin (IL)-1β and IL-18. The activation of these cytokines is usually regulated by the Nucleotide-binding domain, Leucine-rich repeat, and Pyrin domain 3 (NLRP3) inflammasome. ARPE-19 cells were exposed to hydroquinone, and cell viability was monitored using the lactate dehydrogenase (LDH) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide salt (MTT) assays. Enzyme-linked immunosorbent assays (ELISAs) were used to measure the levels of proinflammatory cytokines IL-1β and IL-18 as well as NLRP3, caspase-1, and poly (ADP-ribose) polymerase (PARP). Hydroquinone did not change IL-1β release but significantly increased the secretion of IL-18. Cytoplasmic NLRP3 levels increased after the hydroquinone treatment of IL-1α-primed RPE cells, but IL-18 was equally released from primed and nonprimed cells. Hydroquinone reduced the intracellular levels of PARP, which were restored by treatment with the ROS scavenger N-acetyl-cysteine (NAC). NAC concurrently reduced the NLRP3 levels but had no effect on IL-18 release. In contrast, the NADPH oxidase inhibitor ammonium pyrrolidinedithiocarbamate (APDC) reduced the release of IL-18 but had no effect on the NLRP3 levels. Collectively, hydroquinone caused DNA damage seen as reduced intracellular PARP levels and induced NLRP3-independent IL-18 secretion in human RPE cells. MDPI 2021-06-06 /pmc/articles/PMC8229790/ /pubmed/34204067 http://dx.doi.org/10.3390/cells10061405 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Bhattarai, Niina Korhonen, Eveliina Mysore, Yashavanthi Kaarniranta, Kai Kauppinen, Anu Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells |
title | Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells |
title_full | Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells |
title_fullStr | Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells |
title_full_unstemmed | Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells |
title_short | Hydroquinone Induces NLRP3-Independent IL-18 Release from ARPE-19 Cells |
title_sort | hydroquinone induces nlrp3-independent il-18 release from arpe-19 cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8229790/ https://www.ncbi.nlm.nih.gov/pubmed/34204067 http://dx.doi.org/10.3390/cells10061405 |
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