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Title: Simultaneous activation of innate and adaptive immunity participates in the development of renal injury in a model of heavy proteinuria
Authors: FAUSTINO, Viviane DiasARIAS, Simone Costa AlarconAVILA, Victor FerreiraFORESTO-NETO, OrestesZAMBOM, Fernanda Florencia FregnanMACHADO, Flavia GomesREIS, Luciene Machado dosMARIA, DeniseVOLPINI, Rildo AparecidoCAMARA, Niels Olsen SaraivaZATZ, RobertoFUJIHARA, Clarice Kazue
Citation: BIOSCIENCE REPORTS, v.38, article ID BSR20180762, 18p, 2018
Abstract: Protein overload of proximal tubular cells (PTCs) can promote interstitial injury by unclear mechanisms that may involve activation of innate immunity. We investigated whether prolonged exposure of tubular cells to high protein concentrations stimulates innate immunity, triggering progressive interstitial inflammation and renal injury, and whether specific inhibition of innate or adaptive immunity would provide renoprotection in an established model of massive proteinuria, adriamycin nephropathy (ADR). Adult male Munich-Wistar rats received a single dose of ADR (5 mg/kg, iv), being followed for 2, 4, or 20 weeks. Massive albuminuria was associated with early activation of both the NE-kappa B and NLRP3 innate immunity pathways, whose intensity correlated strongly with the density of lymphocyte infiltration. In addition, ADR rats exhibited clear signs of renal oxidative stress. Twenty weeks after ADR administration, marked interstitial fibrosis, glomerulosclerosis, and renal functional loss were observed. Administration of mycophenolate mofetil (MMF), 10 mg/kg/day, prevented activation of both innate and adaptive immunity, as well as renal oxidative stress and renal fibrosis. Moreover, MMF treatment was associated with shifting of M from the M1 to the M2 phenotype. In cultivated NRK52-E cells, excess albumin increased the protein content of Toll-like receptor (TLR) 4 (TLR4), NLRP3, MCP-1, IL6, IL-1 beta Caspase-1, alpha-actin, and collagen-1. Silencing of TLR4 and/or NLRP3 mRNA abrogated this proinflammatory/profibrotic behavior. Simultaneous activation of innate and adaptive immunity may be key to the development of renal injury in heavy proteinuric disease. Inhibition of specific components of innate and/or adaptive immunity may be the basis for future strategies to prevent chronic kidney disease (CKD) in this setting.
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Artigos e Materiais de Revistas Científicas - FM/MCM
Departamento de Clínica Médica - FM/MCM

Artigos e Materiais de Revistas Científicas - FM/MPT
Departamento de Patologia - FM/MPT

Artigos e Materiais de Revistas Científicas - HC/ICHC
Instituto Central - HC/ICHC

Artigos e Materiais de Revistas Científicas - LIM/05
LIM/05 - Laboratório de Poluição Atmosférica Experimental

Artigos e Materiais de Revistas Científicas - LIM/12
LIM/12 - Laboratório de Pesquisa Básica em Doenças Renais

Artigos e Materiais de Revistas Científicas - LIM/16
LIM/16 - Laboratório de Fisiopatologia Renal

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