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Arthritis Research & Therapy

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Open Access 01-12-2016 | Research article

Nuclear factor erythroid 2-related factor 2 is a critical target for the treatment of glucocorticoid-resistant lupus nephritis

Authors: Shin Ebihara, Hideaki Tajima, Masao Ono

Published in: Arthritis Research & Therapy | Issue 1/2016

Abstract

Background

Dimethyl fumarate (DMF), a nuclear factor erythroid 2-related factor 2 (Nrf2) activator, has been proven effective for the systemic treatment of multiple sclerosis. The aim of this study is to evaluate the anti-inflammatory effects of Nrf2 activators on human renal mesangial cells (HRMCs) and the development of lupus nephritis (LN) in mice.

Methods

To assess Nrf2 activation in vitro, HRMCs were treated with safe doses of Nrf2 activators and prednisolone. The expression levels of Nrf2 and its target genes were measured using quantitative reverse transcription PCR and enzyme-linked immunosorbent assay. The anti-inflammatory effects of these compounds were assessed by measuring tumor necrosis factor alpha-induced cytokine secretion. Experimental LN was induced in female BALB/c mice by a single intraperitoneal injection of pristane. The urine albumin-to-creatinine ratio was measured at 20 weeks after injection. Pathological changes as well as protein and mRNA expression levels were assessed in the kidney obtained at the experimental end point. Oral administration of DMF or prednisolone to these mice was initiated after pristane injection.

Results

Nrf2 activators such as sulforaphane and DMF showed anti-inflammatory effects in HRMCs, whereas glucocorticoid (prednisolone) showed partial effects. Moreover, DMF ameliorated the development of kidney diseases in pristane-induced LN mice, whereas glucocorticoid had no effect.

Conclusions

Nrf2 activators showed stronger anti-inflammatory and organ-protective effects than glucocorticoid in the kidney. Thus, Nrf2 activators are potential therapeutic targets in glucocorticoid-resistant LN in humans.

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Title: Nuclear factor erythroid 2-related factor 2 is a critical target for the treatment of glucocorticoid-resistant lupus nephritis
Authors: Shin Ebihara
Hideaki Tajima
Masao Ono
Publication date: 01-12-2016
Publisher: BioMed Central
Published in: Arthritis Research & Therapy / Issue 1/2016
Electronic ISSN: 1478-6362
DOI: https://doi.org/10.1186/s13075-016-1039-5

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Nuclear factor erythroid 2-related factor 2 is a critical target for the treatment of glucocorticoid-resistant lupus nephritis

Abstract

Background

Methods

Results

Conclusions

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Abstract

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