Local synthesis of interferon-alpha in lupus nephritis is associated with type I interferons signature and LMP7 induction in renal tubular epithelial cells

被引：71

作者：

Castellano, Giuseppe ^{[1
]}

Cafiero, Cesira ^{[1
]}

Divella, Chiara ^{[1
]}

Sallustio, Fabio ^{[2
]}

Gigante, Margherita ^{[1
]}

Pontrelli, Paola ^{[1
]}

De Palma, Giuseppe ^{[2
]}

Rossini, Michele ^{[1
]}

Grandaliano, Giuseppe ^{[3
]}

Gesualdo, Loreto ^{[1
]}

机构：

[1] Univ Bari, Dept Emergency & Organ Transplantat, Renal Dialysis & Transplantat Unit, I-70124 Bari, Italy

[2] CARSO Consortium, Bari, Italy

[3] Univ Foggia, Dept Med & Surg Sci, Renal Dialysis & Transplantat Unit, Foggia, Italy

来源：

ARTHRITIS RESEARCH & THERAPY | 2015年 / 17卷

关键词：

DENDRITIC CELLS; IFN-ALPHA; ERYTHEMATOSUS; PATHOGENESIS; PROTEASOME; PROGRESSION; INHIBITION; MECHANISMS; EXPRESSION; MURINE;

D O I：

10.1186/s13075-015-0588-3

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Introduction: Type I interferons are pivotal in the activation of autoimmune response in systemic lupus erythematous. However, the pathogenic role of interferon-alpha in patients affected by lupus nephritis remains uncertain. The aim of our study was to investigate the presence of a specific interferon signature in lupus nephritis and the effects of interferon-alpha at renal level. Methods: We performed immunohistochemical analysis for MXA-protein and in situ hybridization to detect interferon-alpha signature and production in human lupus nephritis. Through microarray studies, we analyzed the gene expression profile of renal tubular epithelial cells, stimulated with interferon-alpha. We validated microarray results through real-time polymerase chain reaction, flow cytometry on renal tubular epithelial cells, and through immunohistochemical analysis and confocal microscopy on renal biopsies. Results: Type I interferons signature was characterized by MXA-specific staining in renal tubular epithelial cells; in addition, in situ hybridization showed that renal tubular epithelial cells were the major producers of interferon-alpha, indicating a potential autocrine effect. Whole-genome expression profile showed interferon-alpha induced up-regulation of genes involved in innate immunity, protein ubiquitination and switching to immunoproteasome. In accordance with the in vitro data, class IV lupus nephritis showed up-regulation of the immunoproteasome subunit LMP7 in tubular epithelial cells associated with type I interferon signature. Conclusions: Our data indicate that type I interferons might have a pathogenic role in lupus nephritis characterized by an autocrine effect of interferon-alpha on renal tubular epithelial cells. Therefore we hypothesize that inhibition of type I interferons might represent a therapeutic target to prevent tubulo-interstitial damage in patients with lupus nephritis.

引用

页数：12

共 41 条

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