Mitochondrial signaling to control excessive inflammation

Mitochondrial signaling to control excessive inflammation


The 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 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.

The authors 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. 

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

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fmitochondrial-arginase&filter=22

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