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Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis

Crystals cause injury in numerous disorders, and induce inflammation via the NLRP3 inflammasome, however, it remains unclear how crystals induce cell death. Here we report that crystals of calcium oxalate, monosodium urate, calcium pyrophosphate dihydrate and cystine trigger caspase-independent cell...

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Autores principales: Mulay, Shrikant R., Desai, Jyaysi, Kumar, Santhosh V., Eberhard, Jonathan N., Thomasova, Dana, Romoli, Simone, Grigorescu, Melissa, Kulkarni, Onkar P., Popper, Bastian, Vielhauer, Volker, Zuchtriegel, Gabriele, Reichel, Christoph, Bräsen, Jan Hinrich, Romagnani, Paola, Bilyy, Rostyslav, Munoz, Luis E., Herrmann, Martin, Liapis, Helen, Krautwald, Stefan, Linkermann, Andreas, Anders, Hans-Joachim
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738349/
https://www.ncbi.nlm.nih.gov/pubmed/26817517
http://dx.doi.org/10.1038/ncomms10274
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author Mulay, Shrikant R.
Desai, Jyaysi
Kumar, Santhosh V.
Eberhard, Jonathan N.
Thomasova, Dana
Romoli, Simone
Grigorescu, Melissa
Kulkarni, Onkar P.
Popper, Bastian
Vielhauer, Volker
Zuchtriegel, Gabriele
Reichel, Christoph
Bräsen, Jan Hinrich
Romagnani, Paola
Bilyy, Rostyslav
Munoz, Luis E.
Herrmann, Martin
Liapis, Helen
Krautwald, Stefan
Linkermann, Andreas
Anders, Hans-Joachim
author_facet Mulay, Shrikant R.
Desai, Jyaysi
Kumar, Santhosh V.
Eberhard, Jonathan N.
Thomasova, Dana
Romoli, Simone
Grigorescu, Melissa
Kulkarni, Onkar P.
Popper, Bastian
Vielhauer, Volker
Zuchtriegel, Gabriele
Reichel, Christoph
Bräsen, Jan Hinrich
Romagnani, Paola
Bilyy, Rostyslav
Munoz, Luis E.
Herrmann, Martin
Liapis, Helen
Krautwald, Stefan
Linkermann, Andreas
Anders, Hans-Joachim
author_sort Mulay, Shrikant R.
collection PubMed
description Crystals cause injury in numerous disorders, and induce inflammation via the NLRP3 inflammasome, however, it remains unclear how crystals induce cell death. Here we report that crystals of calcium oxalate, monosodium urate, calcium pyrophosphate dihydrate and cystine trigger caspase-independent cell death in five different cell types, which is blocked by necrostatin-1. RNA interference for receptor-interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain like (MLKL), two core proteins of the necroptosis pathway, blocks crystal cytotoxicity. Consistent with this, deficiency of RIPK3 or MLKL prevents oxalate crystal-induced acute kidney injury. The related tissue inflammation drives TNF-α-related necroptosis. Also in human oxalate crystal-related acute kidney injury, dying tubular cells stain positive for phosphorylated MLKL. Furthermore, necrostatin-1 and necrosulfonamide, an inhibitor for human MLKL suppress crystal-induced cell death in human renal progenitor cells. Together, TNF-α/TNFR1, RIPK1, RIPK3 and MLKL are molecular targets to limit crystal-induced cytotoxicity, tissue injury and organ failure.
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spelling pubmed-47383492016-03-04 Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis Mulay, Shrikant R. Desai, Jyaysi Kumar, Santhosh V. Eberhard, Jonathan N. Thomasova, Dana Romoli, Simone Grigorescu, Melissa Kulkarni, Onkar P. Popper, Bastian Vielhauer, Volker Zuchtriegel, Gabriele Reichel, Christoph Bräsen, Jan Hinrich Romagnani, Paola Bilyy, Rostyslav Munoz, Luis E. Herrmann, Martin Liapis, Helen Krautwald, Stefan Linkermann, Andreas Anders, Hans-Joachim Nat Commun Article Crystals cause injury in numerous disorders, and induce inflammation via the NLRP3 inflammasome, however, it remains unclear how crystals induce cell death. Here we report that crystals of calcium oxalate, monosodium urate, calcium pyrophosphate dihydrate and cystine trigger caspase-independent cell death in five different cell types, which is blocked by necrostatin-1. RNA interference for receptor-interacting protein kinase 3 (RIPK3) or mixed lineage kinase domain like (MLKL), two core proteins of the necroptosis pathway, blocks crystal cytotoxicity. Consistent with this, deficiency of RIPK3 or MLKL prevents oxalate crystal-induced acute kidney injury. The related tissue inflammation drives TNF-α-related necroptosis. Also in human oxalate crystal-related acute kidney injury, dying tubular cells stain positive for phosphorylated MLKL. Furthermore, necrostatin-1 and necrosulfonamide, an inhibitor for human MLKL suppress crystal-induced cell death in human renal progenitor cells. Together, TNF-α/TNFR1, RIPK1, RIPK3 and MLKL are molecular targets to limit crystal-induced cytotoxicity, tissue injury and organ failure. Nature Publishing Group 2016-01-28 /pmc/articles/PMC4738349/ /pubmed/26817517 http://dx.doi.org/10.1038/ncomms10274 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Mulay, Shrikant R.
Desai, Jyaysi
Kumar, Santhosh V.
Eberhard, Jonathan N.
Thomasova, Dana
Romoli, Simone
Grigorescu, Melissa
Kulkarni, Onkar P.
Popper, Bastian
Vielhauer, Volker
Zuchtriegel, Gabriele
Reichel, Christoph
Bräsen, Jan Hinrich
Romagnani, Paola
Bilyy, Rostyslav
Munoz, Luis E.
Herrmann, Martin
Liapis, Helen
Krautwald, Stefan
Linkermann, Andreas
Anders, Hans-Joachim
Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis
title Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis
title_full Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis
title_fullStr Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis
title_full_unstemmed Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis
title_short Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis
title_sort cytotoxicity of crystals involves ripk3-mlkl-mediated necroptosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4738349/
https://www.ncbi.nlm.nih.gov/pubmed/26817517
http://dx.doi.org/10.1038/ncomms10274
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