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Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19
As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cyto...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177105/ https://www.ncbi.nlm.nih.gov/pubmed/37174682 http://dx.doi.org/10.3390/cells12091282 |
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author | Paunovic, Verica Vucicevic, Ljubica Misirkic Marjanovic, Maja Perovic, Vladimir Ristic, Biljana Bosnjak, Mihajlo Mandic, Milos Stevanovic, Danijela Harhaji-Trajkovic, Ljubica Lalosevic, Jovan Nikolic, Milos Bonaci-Nikolic, Branka Trajkovic, Vladimir |
author_facet | Paunovic, Verica Vucicevic, Ljubica Misirkic Marjanovic, Maja Perovic, Vladimir Ristic, Biljana Bosnjak, Mihajlo Mandic, Milos Stevanovic, Danijela Harhaji-Trajkovic, Ljubica Lalosevic, Jovan Nikolic, Milos Bonaci-Nikolic, Branka Trajkovic, Vladimir |
author_sort | Paunovic, Verica |
collection | PubMed |
description | As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation. |
format | Online Article Text |
id | pubmed-10177105 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-101771052023-05-13 Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19 Paunovic, Verica Vucicevic, Ljubica Misirkic Marjanovic, Maja Perovic, Vladimir Ristic, Biljana Bosnjak, Mihajlo Mandic, Milos Stevanovic, Danijela Harhaji-Trajkovic, Ljubica Lalosevic, Jovan Nikolic, Milos Bonaci-Nikolic, Branka Trajkovic, Vladimir Cells Article As autophagy can promote or inhibit inflammation, we examined autophagy-inflammation interplay in COVID-19. Autophagy markers in the blood of 19 control subjects and 26 COVID-19 patients at hospital admission and one week later were measured by ELISA, while cytokine levels were examined by flow cytometric bead immunoassay. The antiviral IFN-α and proinflammatory TNF, IL-6, IL-8, IL-17, IL-33, and IFN-γ were elevated in COVID-19 patients at both time points, while IL-10 and IL-1β were increased at admission and one week later, respectively. Autophagy markers LC3 and ATG5 were unaltered in COVID-19. In contrast, the concentration of autophagic cargo receptor p62 was significantly lower and positively correlated with TNF, IL-10, IL-17, and IL-33 at hospital admission, returning to normal levels after one week. The expression of SARS-CoV-2 proteins NSP5 or ORF3a in THP-1 monocytes caused an autophagy-independent decrease or autophagy-inhibition-dependent increase, respectively, of intracellular/secreted p62, as confirmed by immunoblot/ELISA. This was associated with an NSP5-mediated decrease in TNF/IL-10 mRNA and an ORF3a-mediated increase in TNF/IL-1β/IL-6/IL-10/IL-33 mRNA levels. A genetic knockdown of p62 mimicked the immunosuppressive effect of NSP5, and a p62 increase in autophagy-deficient cells mirrored the immunostimulatory action of ORF3a. In conclusion, the proinflammatory autophagy receptor p62 is reduced inacute COVID-19, and the balance between autophagy-independent decrease and autophagy blockade-dependent increase of p62 levels could affect SARS-CoV-induced inflammation. MDPI 2023-04-28 /pmc/articles/PMC10177105/ /pubmed/37174682 http://dx.doi.org/10.3390/cells12091282 Text en © 2023 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 Paunovic, Verica Vucicevic, Ljubica Misirkic Marjanovic, Maja Perovic, Vladimir Ristic, Biljana Bosnjak, Mihajlo Mandic, Milos Stevanovic, Danijela Harhaji-Trajkovic, Ljubica Lalosevic, Jovan Nikolic, Milos Bonaci-Nikolic, Branka Trajkovic, Vladimir Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19 |
title | Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19 |
title_full | Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19 |
title_fullStr | Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19 |
title_full_unstemmed | Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19 |
title_short | Autophagy Receptor p62 Regulates SARS-CoV-2-Induced Inflammation in COVID-19 |
title_sort | autophagy receptor p62 regulates sars-cov-2-induced inflammation in covid-19 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10177105/ https://www.ncbi.nlm.nih.gov/pubmed/37174682 http://dx.doi.org/10.3390/cells12091282 |
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