Nur77: Key Functions and Therapeutic Prospects in Inflammation-Related Lung Diseases.

Nur77: Key Functions and Therapeutic Prospects in Inflammation-Related Lung Diseases. Am J Pathol. 2018 Nov 07;: Authors: Banno A, Lakshmi SP, Reddy AT, Kim SC, Reddy RC Abstract The transcription factor nuclear receptor 77 (Nur77) belongs to the NR4A subfamily of nuclear hormone receptors. It features an atypical ligand-binding site that precludes canonical ligand binding, leading to the designation "orphan nuclear receptor." However, recent studies show that small molecules can interact with the receptor and modulate its activity by inducing a conformational change in the Nur77 ligand-binding site. Nur77 expression and activation are rapidly induced by a wide range of physiological and pathological stimuli. Once expressed, Nur77 initiates transcriptional activity and modulates expression of its target genes. Both in vitro and in vivo evidence shows that Nur77 dampens the immune response to pro-inflammatory stimuli such as tumor necrosis factor-α, toll-like receptor ligands, and oxidized lipids, primarily by suppressing NF-κB signaling. Although studies focusing on Nur77's role in lung pathophysiology are currently incomplete, available data support its involvement in the pathogenesis of several lung diseases including asthma, acute lung injury, and pulmonary fibrosis, and thus suggest a therapeutic potential for Nur77 activation in these diseases. This review addresses the mechanisms that control Nur77 expression and activity as ...
Source: The American Journal of Pathology - Category: Pathology Authors: Tags: Am J Pathol Source Type: research