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
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Additional Information: | Copyright of this article belongs to ASBMB. |
| Uncontrolled Keywords: | gene transcription; inflammation;macrophage ; nuclear receptor sepsis Arginase 1; |
| Subjects: | Q Science > QR Microbiology |
| Depositing User: | Dr. K.P.S.Sengar |
| Date Deposited: | 28 Jan 2016 11:13 |
| Last Modified: | 28 Jan 2016 11:13 |
| URI: | http://crdd.osdd.net/open/id/eprint/1769 |
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