NLRP3 inflammasome: Pathogenic role and potential therapeutic target for IgA nephropathy.
Sci Rep
; 7: 41123, 2017 01 24.
Article
en En
| MEDLINE
| ID: mdl-28117341
ABSTRACT
We have previously showed that IL-1ß is involved in the pathogenesis of both spontaneously occurring and passively induced IgA nephropathy (IgAN) models. However, the exact causal-relationship between NLRP3 inflammasome and the pathogenesis of IgAN remains unknown. In the present study, we showed that [1] IgA immune complexes (ICs) activated NLRP3 inflammasome in macrophages involving disruption of mitochondrial integrity and induction of mitochondrial ROS, bone marrow-derived dendritic cells (BMDCs) and renal intrinsic cells; [2] knockout of NLRP3 inhibited IgA ICs-mediated activation of BMDCs and T cells; and [3] knockout of NLRP3 or a kidney-targeting delivery of shRNA of NLRP3 improved renal function and renal injury in a mouse IgAN model. These results strongly suggest that NLRP3 inflammasome serves as a key player in the pathogenesis of IgAN partly through activation of T cells and mitochondrial ROS production and that a local, kidney-targeting suppression of NLRP3 be a therapeutic strategy for IgAN.
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Inflamasomas
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Proteína con Dominio Pirina 3 de la Familia NLR
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Glomerulonefritis por IGA
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Macrófagos
Idioma:
En
Revista:
Sci Rep
Año:
2017
Tipo del documento:
Article