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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Biosci+Rep
2018 ; 38
(4
): ä Nephropedia Template TP
gab.com Text
Twit Text FOAVip
Twit Text #
English Wikipedia
Simultaneous activation of innate and adaptive immunity participates in the
development of renal injury in a model of heavy proteinuria
#MMPMID29914975
Faustino VD
; Arias SCA
; Ferreira Ávila V
; Foresto-Neto O
; Zambom FFF
; Machado FG
; Machado Dos Reis L
; Malheiros DMAC
; Volpini RA
; Camara NOS
; Zatz R
; Fujihara CK
Biosci Rep
2018[Aug]; 38
(4
): ä PMID29914975
show ga
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 NF-?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?,
Caspase-1, ?-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.
|*Adaptive Immunity/drug effects
[MESH]
|*Immunity, Innate/drug effects
[MESH]
|Acute Kidney Injury/*etiology/*immunology/pathology/prevention & control
[MESH]