Oncotarget

Research Papers:

Orphan nuclear receptor Nur77 inhibits poly (I:C)-triggered acute liver inflammation by inducing the ubiquitin-editing enzyme A20

Xiu-Ming Li, Tian-Yu Yang, Xiao-Shun He, Jing-Ru Wang, Wen-Juan Gan, Shen Zhang, Jian-Ming Li and Hua Wu _

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Oncotarget. 2017; 8:61025-61035. https://doi.org/10.18632/oncotarget.17731

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Abstract

Xiu-Ming Li1,*, Tian-Yu Yang1,*, Xiao-Shun He2,*, Jing-Ru Wang1, Wen-Juan Gan2, Shen Zhang1, Jian-Ming Li1 and Hua Wu1

1Pathology Center and Department of Pathology, Soochow University, Suzhou 215123, China

2Department of Pathology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou 215006, China

*These authors have contributed equally to this work

Correspondence to:

Hua Wu, email: wuhua@suda.edu.cn

Jian-Ming Li, email: jianmingli@suda.edu.cn

Keywords: Nur77, liver inflammation, NF-κB, A20, mouse model

Received: March 23, 2017     Accepted: April 12, 2017     Published: May 09, 2017

ABSTRACT

Inflammation is a key contributor to various types of acute and chronic liver disease. We recently reported that lack of Nur77, an orphan nuclear receptor, contributes to the pathogenesis of inflammatory diseases including inflammatory bowel disease and sepsis. However, whether Nur77 plays a critical role in liver inflammation remains to be fully understood. Employing in vivo acute liver inflammation model in wild-type (Nur77+/+) and Nur77-/- mice, we here found that Nur77 deficiency dramatically increased the production of pro-inflammatory cytokines and accelerated liver injury induced by poly (I:C)/D-GalN in Nur77-/- mice. Mechanistically, Nur77 acts as a negative regulator of NF-κB signaling by inducing the expression of ubiquitin-editing enzyme A20, a novel target gene of Nur77. Notably, in inflammatory cells, overexpression of A20 enhanced, whereas knockdown of A20 by siRNA approach impaired, the inhibitory effect of Nur77 on poly (I:C)-triggered inflammation. Collectively, our data suggest that the orphan nuclear receptor Nur77 plays a protective role in poly (I:C)-triggered liver inflammation by inducing A20, thus making it a promising target for the prevention and treatment of liver inflammation.


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