Mulay SR, Desai J, Kumar SV, Eberhard JN, Thomasova D, Romoli S, Grigorescu M, Kulkarni OP, Popper B, Vielhauer V, Zuchtriegel G, Reichel C, Braesen JH, Romagnani P, Bilyy R, Munoz LE, Herrmann M, Liapis H, Krautwald S, Linkermann A, Anders HJ (2016)
Publication Type: Journal article
Publication year: 2016
Book Volume: 7
Pages Range: 10274
DOI: 10.1038/ncomms10274
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-?-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-?/TNFR1, RIPK1, RIPK3 and MLKL are molecular targets to limit crystal-induced cytotoxicity, tissue injury and organ failure.
APA:
Mulay, S.R., Desai, J., Kumar, S.V., Eberhard, J.N., Thomasova, D., Romoli, S.,... Anders, H.-J. (2016). Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis. Nature Communications, 7, 10274. https://doi.org/10.1038/ncomms10274
MLA:
Mulay, Shrikant R., et al. "Cytotoxicity of crystals involves RIPK3-MLKL-mediated necroptosis." Nature Communications 7 (2016): 10274.
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