Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782413595456307200 |
---|---|
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. |
format | Online Article Text |
id | pubmed-4738349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT mulayshrikantr cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT desaijyaysi cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT kumarsanthoshv cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT eberhardjonathann cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT thomasovadana cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT romolisimone cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT grigorescumelissa cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT kulkarnionkarp cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT popperbastian cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT vielhauervolker cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT zuchtriegelgabriele cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT reichelchristoph cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT brasenjanhinrich cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT romagnanipaola cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT bilyyrostyslav cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT munozluise cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT herrmannmartin cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT liapishelen cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT krautwaldstefan cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT linkermannandreas cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis AT andershansjoachim cytotoxicityofcrystalsinvolvesripk3mlklmediatednecroptosis |