Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Ulrich, Christof, Kneser, Leonie, Fiedler, Roman, Beckert, Julia, Wildgrube, Susann, Seibert, Eric, Fick, Sylvia, Schäfer, Christoph, Markau, Silke, Trojanowicz, Bogusz, Girndt, Matthias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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
_version_ 1784621794817212416
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
work_keys_str_mv AT ulrichchristof pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT kneserleonie pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT fiedlerroman pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT beckertjulia pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT wildgrubesusann pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT seiberteric pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT ficksylvia pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT schaferchristoph pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT markausilke pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT trojanowiczbogusz pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients
AT girndtmatthias pyroptosisacommonfeatureofimmunecellsofhaemodialysispatients