Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and Confers Protection in Sepsis.
IR@IMTECH: CSIR-Institute of Microbial Technology, Chandigarh
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| Title |
Nuclear Receptor Nr4a2 Promotes Alternative Polarization of Macrophages and Confers Protection in Sepsis.
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| Creator |
Mahajan, Sahil
Saini, Ankita Chandra, Vemika Nanduri, Ravikanth Kalra, Rashi Bhagyaraj, Ella Khatri, Neeraj Gupta, Pawan |
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| Subject |
QR Microbiology
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| Description |
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.
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| Publisher |
ASBMB
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| Date |
2015-07-24
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| Type |
Article
PeerReviewed |
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| Relation |
http://www.jbc.org/content/early/2015/05/07/jbc.M115.638064
http://crdd.osdd.net/open/1769/ |
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| Identifier |
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
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