Pyroptosis: A Common Feature of Immune Cells of Haemodialysis Patients

Autor: Susann Wildgrube, Leonie Kneser, Julia Beckert, Christof Ulrich, Roman Fiedler, Christoph Schäfer, Bogusz Trojanowicz, Sylvia Fick, Eric Seibert, Silke Markau, Matthias Girndt
Rok vydání: 2021
Předmět:
Zdroj: Toxins; Volume 13; Issue 12; Pages: 839
Toxins
Toxins, Vol 13, Iss 839, p 839 (2021)
ISSN: 2072-6651
DOI: 10.3390/toxins13120839
Popis: 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.
Databáze: OpenAIRE
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