Arginase 2, iNOS, macrophage polarizarion - brief notes

Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages 

 https://www.nature.com/articles/s41467-021-21617-2

 

" ‘M1-like’ inflammatory macrophages utilize aerobic glycolysis for the generation of ATP. This is accompanied with a downregulation of mitochondrial oxidative phosphorylation (OxPhos) and an accumulation of certain metabolites in the tricarboxylic acid (TCA) cycle, such as citrate and succinate2,3.

IL-10 increases arginase expression to limit the availability of arginine for NO production13,17. In fact, IL-10 was shown to regulate macrophage glycolytic commitment by preserving OxPhos through its suppression of NO18 or via suppression of mammalian target of rapamycin (mTOR)19. It has also been shown that IL-10, via STAT3, inhibits the pro-inflammatory microRNA miR-15520. IL-10 was shown to modulate miR-155 target genes suggesting a distinct mechanism that IL-10 uses to maintain an anti-inflammatory state in macrophages20.

Here, we identify Arg2 as one of the most prominent metabolic genes regulated by the IL-10/miR-155 axis. We also show that IL-10-mediated induction of Arg2 protein is essential for skewing mitochondrial dynamics and bioenergetics in inflammatory macrophages towards an oxidative phenotype, particularly by enhancing activity of complex II (CII) at the electron transport chain (ETC). This work highlights Arg2 as a downstream mediator of IL-10 and provides a mechanism for its function as a resolver of inflammation."

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