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Summary: The protein Arginase-2 works through mitochondria to reduce inflammation. The findings could lead to new treatments for diseases associated with neuroinflammation, including multiple sclerosis and rheumatoid arthritis.
Source: RCSI
RCSI researchers have discovered a new way to ‘put the brakes’ on excessive inflammation by regulating a type of white blood cell that is critical for our immune system.
The discovery has the potential to protect the body from unchecked damage caused by inflammatory diseases.
The paper, led by researchers at RCSI University of Medicine and Health Sciences, is published in Nature Communications.
When immune cells (white blood cells) in our body called macrophages are exposed to potent infectious agents, powerful inflammatory proteins known as cytokines are produced to fight the invading infection. However, if these cytokine levels get out of control, significant tissue damage can occur.
The researchers have found that a protein called Arginase-2 works through the energy source of macrophage cells, known as mitochondria, to limit inflammation. Specifically they have shown for the first time that Arginase-2 is critical for decreasing a potent inflammatory cytokine called IL-1.
This discovery could allow researchers to develop new treatments that target the Arginase-2 protein and protect the body from unchecked damage caused by inflammatory diseases.
“Excessive inflammation is a prominent feature of many diseases such as multiple sclerosis, arthritis and inflammatory bowel diseases. Through our discovery, we may be able to develop novel therapeutics for the treatment of inflammatory disease and ultimately improve the quality of life for people with these conditions,” commented senior author on the paper Dr Claire McCoy, Senior Lecturer in Immunology at RCSI.
The study was led by researchers at the School of Pharmacy and Biomolecular Sciences, RCSI (Dr Claire McCoy, Dr Jennifer Dowling and Ms Remsha Afzal) in collaboration with a network of international researchers from Australia, Germany, and Switzerland.
Funding: The research was funded by Science Foundation Ireland, with initial stages of the research originating from a grant from the National Health Medical Research Council, Australia.
About this inflammation research news
Source: RCSI
Contact: Press Office – RCSI
Image: The image is in the public domain
Original Research: Open access.
“Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages” by Jennifer K. Dowling, Remsha Afzal, Linden J. Gearing, Mariana P. Cervantes-Silva, Stephanie Annett, Gavin M. Davis, Chiara De Santi, Nadine Assmann, Katja Dettmer, Daniel J. Gough, Glenn R. Bantug, Fidinny I. Hamid, Frances K. Nally, Conor P. Duffy, Aoife L. Gorman, Alex M. Liddicoat, Ed C. Lavelle, Christoph Hess, Peter J. Oefner, David K. Finlay, Gavin P. Davey, Tracy Robson, Annie M. Curtis, Paul J. Hertzog, Bryan R. G. Williams & Claire E. McCoy. Nature Communications
Abstract
See also
Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages
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 1α (HIF-1α) and IL-1β in vitro. Accordingly, HIF-1α and IL-1β 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.
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