title: NLRP3 inflammasome: Pathogenic role and potential therapeutic target for IgA nephropathy.
abstract: We have previously showed that IL-1β 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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Tsai
authors.affiliation: Department of Biotechnology and Animal Science, National Ilan University, Ilan, Taiwan, ROC.
authors.forename: Kuo-Feng
authors.initials: KF
authors.lastname: Hua
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Ann
authors.initials: A
authors.lastname: Chen
authors.affiliation: Department of Nutrition, Hungkuang University, Taichung, Taiwan, ROC.
authors.forename: Chyou-Wei
authors.initials: CW
authors.lastname: Wei
authors.affiliation: Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
authors.forename: Wen-Shiang
authors.initials: WS
authors.lastname: Chen
authors.affiliation: Molecular Genetics Laboratory, Department of Microbiology and Immunology, Chang-Gung University, Taoyuan, Taiwan, ROC.
authors.forename: Cheng-Yeu
authors.initials: CY
authors.lastname: Wu
authors.affiliation: Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan, ROC.
authors.forename: Ching-Liang
authors.initials: CL
authors.lastname: Chu
authors.affiliation: Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Yung-Luen
authors.initials: YL
authors.lastname: Yu
authors.affiliation: Department of Physical Medicine and Rehabilitation, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan, ROC.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Lo
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, ROC.|Graduate Institute of Aerospace and Undersea Medicine, Academy of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC.
authors.forename: Shuk-Man
authors.initials: SM
authors.lastname: Ka
mesh_terms: D000818:Animals; D005260:Female; D005922:Glomerulonephritis, IGA / Q000276:immunology / Q000378:metabolism*; D058847:Inflammasomes / Q000378:metabolism*; D007668:Kidney / Q000276:immunology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species