creators_name: Mahajan, Sahil
creators_name: Saini, Ankita
creators_name: Chandra, Vemika
creators_name: Nanduri, Ravikanth
creators_name: Kalra, Rashi
creators_name: Bhagyaraj, Ella
creators_name: Khatri, Neeraj
creators_name: Gupta, Pawan
type: article
datestamp: 2016-01-28 11:13:29
lastmod: 2016-01-28 11:13:29
metadata_visibility: show
title: Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and Confers Protection in Sepsis.
ispublished: pub
subjects: QR
keywords: gene transcription; inflammation;macrophage ;
nuclear receptor
sepsis
Arginase 1;
note: Copyright of this article belongs to ASBMB.
abstract: The orphan nuclear receptor Nr4a2 is known to modulate both inflammatory and metabolic processes, but the mechanism by which it regulates innate inflammatory homeostasis has not been adequately addressed. This study shows that exposure to ligands for Toll-like receptors (TLRs) robustly induces Nr4a2 and that this induction is tightly regulated by the PI3K-Akt signaling axis. Interestingly, exogenous expression of Nr4a2 in macrophages leads to their alternative phenotype with induction of genes that are prototypical M2 markers. Moreover, Nr4a2 transcriptionally activates arginase 1 expression by directly binding to its promoter. Adoptive transfer experiments revealed that increased survival of animals in endotoxin-induced sepsis is Nr4a2-dependent. Thus our data identify a previously unknown role for Nr4a2 in the regulation of macrophage polarization.
date: 2015-07-24
date_type: published
publication: The Journal of biological chemistry
volume: 290
number: 30
publisher: ASBMB
pagerange: 18304-14
refereed: TRUE
issn: 1083-351X
official_url: http://www.jbc.org/content/early/2015/05/07/jbc.M115.638064
citation:   Mahajan, Sahil and Saini, Ankita and Chandra, Vemika and Nanduri, Ravikanth and Kalra, Rashi and Bhagyaraj, Ella and Khatri, Neeraj and Gupta, Pawan  (2015) Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and Confers Protection in Sepsis.  The Journal of biological chemistry, 290 (30).  pp. 18304-14.  ISSN 1083-351X