Itaconate is a potential anti–inflammatory
Biologists have learned to regulate the immune response of macrophages
Scientists from the USA, Canada, Germany and Russia have found a substance capable of suppressing the action of macrophages – one of the types of cells of the immune system. It turned out to be itaconate, which is produced by macrophages themselves. Its anti-inflammatory effect can be used to treat pathologies associated with excessive inflammation. The scientists' article was published in the journal Cell Metabolism (Lampropoulou et al., Itaconate Links Inhibition of Succinate Dehydrogenase with Macrophage Metabolic Remodeling and Regulation of Inflammation).
Russian scientists from ITMO University together with colleagues studied macrophages – one of the types of cells of the immune system that are responsible for eliminating pathogens in the body. They are the first to arrive to fight infections and after the transition to an active state associated with the activation of certain molecular mechanisms, they begin to capture and digest pathogenic bacteria. However, sometimes macrophages get too carried away in their work, which leads to excessive development of the inflammatory process and negative consequences for the whole organism.
Scientists have studied how macrophages transition from an inactive state to a pro-inflammatory one, and found that the substance itaconate suppresses excessive diligence of macrophages. At the same time, it is produced by the activating macrophages themselves.
"Itaconate sets a certain bar for macrophages: when its concentration exceeds a certain limit, the activation of macrophages slows down," says Alexey Sergushichev, one of the authors of the article and a graduate student at ITMO University. – Without this substance, the inflammatory process would increase more than required. In the future, with the help of itaconate, it is possible to artificially control the activation of macrophages, which means to restrain the intensity of inflammation."
Itaconate interrupts the circulation of substances in the macrophage cell
to generate energy by suppressing the Sdh enzyme.
The drawing is provided by the ITMO press service.
The action of itaconate is based on the fact that it can interrupt the Krebs cycle – a set of biochemical reactions associated with cellular respiration and located at the intersection of metabolic pathways. Among other things, it suppresses the enzyme Sdh (succinate dehydrogenase), which not only participates in the cycle, but also binds it to signaling pathways for information exchange between macrophages. Therefore, blocking Sdh slows down the activation of macrophages.
According to scientists, itaconate produced by the body itself is safe for health and can be useful for the treatment of various pathologies associated with excessive inflammation, for example, in coronary heart disease, liver, kidneys, as well as metabolic disorders and possibly autoimmune diseases.
Now researchers are testing the effect of itaconate on living organisms. The first experiments showed that this substance reduces damage to the heart muscle in myocardial infarction in mice, but in order to transfer this method to the human body, according to the researchers, further work is needed.
The use of itaconate is not the only way to regulate the immune response of macrophages. Earlier, scientists of the same scientific group showed that the process of macrophage activation strongly depends on the concentration of the amino acid glutamine.
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05.07.2016