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Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients
NLRP-3 inflammasome activation can result in interleukin-1β (IL-1β) release and inflammatory cell death (pyroptosis). Caspase-1 is able to trigger both processes. However, other caspases, caspase-4, -5 and -8, are believed to initiate pyroptosis without affecting IL-1 secretion. In this study, we ev...
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/PMC8704801/ https://www.ncbi.nlm.nih.gov/pubmed/34941677 http://dx.doi.org/10.3390/toxins13120839 |
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author | Ulrich, Christof Kneser, Leonie Fiedler, Roman Beckert, Julia Wildgrube, Susann Seibert, Eric Fick, Sylvia Schäfer, Christoph Markau, Silke Trojanowicz, Bogusz Girndt, Matthias |
author_facet | Ulrich, Christof Kneser, Leonie Fiedler, Roman Beckert, Julia Wildgrube, Susann Seibert, Eric Fick, Sylvia Schäfer, Christoph Markau, Silke Trojanowicz, Bogusz Girndt, Matthias |
author_sort | Ulrich, Christof |
collection | PubMed |
description | NLRP-3 inflammasome activation can result in interleukin-1β (IL-1β) release and inflammatory cell death (pyroptosis). Caspase-1 is able to trigger both processes. However, other caspases, caspase-4, -5 and -8, are believed to initiate pyroptosis without affecting IL-1 secretion. In this study, we evaluated two cardiovascular risk groups, haemodialysis patients (HD) and patients with intact kidney function but high blood pressure (BP), to analyse the mechanisms driving pyroptosis. Twenty HD were age-, gender- and diabetes-matched to BP. We found a common pyroptotic pattern in both patient groups, at which pyroptosis rates but not IL-1 β levels were significantly higher in monocytes (HD vs. BP: p < 0.05), granulocytes (p < 0.01) and lymphocytes (p < 0.01) of HD patients. As uremic toxins are drivers of inflammation and regulated cell death, we applied a monocyte- and macrophage-like THP-1 model system to demonstrate that the protein-bound uremic toxin indoxyl sulfate (IS) is an inducer of pyroptotic cell death, particularly engaging caspase-4/caspase-5 and to a lesser extent caspase-8 and caspase-1. These data suggest that the uremic toxin IS can mediate pyroptosis in HD patients and the inflammatory caspase-4 and/or caspase-5 contribute to pyroptosis rates to a higher extent in comparison to caspase-1. |
format | Online Article Text |
id | pubmed-8704801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87048012021-12-25 Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients Ulrich, Christof Kneser, Leonie Fiedler, Roman Beckert, Julia Wildgrube, Susann Seibert, Eric Fick, Sylvia Schäfer, Christoph Markau, Silke Trojanowicz, Bogusz Girndt, Matthias Toxins (Basel) Article NLRP-3 inflammasome activation can result in interleukin-1β (IL-1β) release and inflammatory cell death (pyroptosis). Caspase-1 is able to trigger both processes. However, other caspases, caspase-4, -5 and -8, are believed to initiate pyroptosis without affecting IL-1 secretion. In this study, we evaluated two cardiovascular risk groups, haemodialysis patients (HD) and patients with intact kidney function but high blood pressure (BP), to analyse the mechanisms driving pyroptosis. Twenty HD were age-, gender- and diabetes-matched to BP. We found a common pyroptotic pattern in both patient groups, at which pyroptosis rates but not IL-1 β levels were significantly higher in monocytes (HD vs. BP: p < 0.05), granulocytes (p < 0.01) and lymphocytes (p < 0.01) of HD patients. As uremic toxins are drivers of inflammation and regulated cell death, we applied a monocyte- and macrophage-like THP-1 model system to demonstrate that the protein-bound uremic toxin indoxyl sulfate (IS) is an inducer of pyroptotic cell death, particularly engaging caspase-4/caspase-5 and to a lesser extent caspase-8 and caspase-1. These data suggest that the uremic toxin IS can mediate pyroptosis in HD patients and the inflammatory caspase-4 and/or caspase-5 contribute to pyroptosis rates to a higher extent in comparison to caspase-1. MDPI 2021-11-25 /pmc/articles/PMC8704801/ /pubmed/34941677 http://dx.doi.org/10.3390/toxins13120839 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 Ulrich, Christof Kneser, Leonie Fiedler, Roman Beckert, Julia Wildgrube, Susann Seibert, Eric Fick, Sylvia Schäfer, Christoph Markau, Silke Trojanowicz, Bogusz Girndt, Matthias Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients |
title | Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients |
title_full | Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients |
title_fullStr | Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients |
title_full_unstemmed | Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients |
title_short | Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients |
title_sort | pyroptosis: a common feature of immune cells of haemodialysis patients |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8704801/ https://www.ncbi.nlm.nih.gov/pubmed/34941677 http://dx.doi.org/10.3390/toxins13120839 |
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