Dowling, Jennifer K. and Afzal, Remsha and Gearing, Linden J. and Cervantes-Silva, Mariana P. and Annett, Stephanie and Davis, Gavin M. and De Santi, Chiara and Assmann, Nadine and Dettmer, Katja and Gough, Daniel J. and Bantug, Glenn R. and Hamid, Fidinny and Nally, Frances K. and Duffy, Conor P. and Gorman, Aoife L. and Liddicoat, Alex M. and Lavelle, Ed C. and Hess, Christoph and Oefner, Peter J. and Finlay, David K. and Davey, Gavin P. and Robson, Tracy and Curtis, Annie M. and Hertzog, Paul J. and Williams, Bryan R. G. and McCoy, Claire E. (2021) Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages. NATURE COMMUNICATIONS, 12 (1): 1460. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)Abstract
Mitochondria are important regulators of macrophage polarisation. Here, we show that arginase-2 (Arg2) is a microRNA-155 (miR-155) and interleukin-10 (IL-10) regulated protein localized at the mitochondria in inflammatory macrophages, and is critical for IL-10-induced modulation of mitochondrial dynamics and oxidative respiration. Mechanistically, the catalytic activity and presence of Arg2 at the mitochondria is crucial for oxidative phosphorylation. We further show that Arg2 mediates this process by increasing the activity of complex II (succinate dehydrogenase). Moreover, Arg2 is essential for IL-10-mediated downregulation of the inflammatory mediators succinate, hypoxia inducible factor 1 alpha (HIF-1 alpha) and IL-1 beta in vitro. Accordingly, HIF-1 alpha and IL-1 beta are highly expressed in an LPS-induced in vivo model of acute inflammation using Arg2(-/-) mice. These findings shed light on a new arm of IL-10-mediated metabolic regulation, working to resolve the inflammatory status of the cell. IL-10 can limit inflammation in part by inhibiting miR-155. Here the authors show how this axis induces mitochondrial arginase-2 to alter the mitochondrial dynamics and bioenergetics of macrophages and make these cells less pro-inflammatory.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Funktionelle Genomik (Prof. Oefner) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Sep 2022 14:12 |
| Last Modified: | 21 Sep 2022 14:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47892 |
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