Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Natural metabolite can suppress inflammation

01.07.2016

An international group of scientists from US, Canada, Germany and Russia has revealed a substance produced in humans that can suppress the pro-inflammatory activity of macrophages - specific cells of immune system. The substance known as itaconate is released in large quantities by macrophages themselves, but until now its role remained poorly studied.

Now scientists have found evidence that itaconate acts as an antioxidant and anti-inflammatory agent. These properties make itaconate promising for the treatment of pathologies caused by excessive inflammation or oxidative stress. Such conditions may be associated with cardiac ischemia, metabolic disorders and perhaps autoimmune diseases. The findings were published in Cell Metabolism.


The was image inspired by draw-bridges of Saint Petersburg depicts Itaconate disrupting the TCA cycle flow.

Credit: © Aleksandra Ziminova

The work, which united scientists from Washington University in St. Louis, ITMO University, McGill University and Max Planck Institute of Immunobiology and Epigenetics, was based on the study of macrophages - immune system cells in charge of fighting pathogens.

An important feature of macrophages is their ability to switch between different states depending on the concentration of various substances in the body. In total, there are three such states: M0 - neutral, M1 - pro-inflammatory and M2 anti-inflammatory.

M1 macrophages are the first who arrive to fight the infection. As they begin to swallow viruses and bacteria, an intense inflammatory process kicks in. This process may adversely affect the entire organism if the macrophages become overly diligent.

Inflammation consumes energy resources of the organism and can lead to numerous complications or even death. That is why in order to mitigate the negative consequences of immune response, it is important to understand how we can reduce the excessive proinflammatory effect of macrophages.

An in-depth study of macrophage metabolism during their transition from inactive to proinflammatory state helped researchers identify the substance that could suppress macrophage-related inflammations. Describing the working mechanism of this substance called itaconate became possible due to a complex map of metabolic pathways in macrophages that was developed by the group.

Itaconate is produced by macrophages when they switch from M0 inactive state to M1 pro-inflammatory state. If the concentration of this substance increases to defined limit, macrophage activation falls. "Itaconate sets the bar controlling M1 macrophage formation," says Alexey Sergushichev, one of the authors of the paper and PhD student at ITMO University.

"Without this substance, the inflammation would increase more than required. In the future, with the help of itaconate, it will be possible to artificially manipulate the transition of macrophages from M0 to M1, meaning the possibility of restraining inflammations. The influence of itaconate on macrophages is a delicate mechanism that can ensure high selectivity of the immune system regulation."

Prior to the study, guesswork with respect to the function and origin of itaconate generated a lot of speculations. But the new study shows that itaconate plays the role of immune regulator. To understand how itaconate reduces the activity of immune cells, the researchers examined the so-called Krebs cycle, or tricarboxylic acid cycle and cellular respiration (processes of producing of vital substances and energy from the oxidation of glucose in cells). Having done so, the scientists identified two "bottlenecks" that can be influenced to reverse the reaction and send it another way.

The Krebs cycle is preceded by signal transmission between cells through oxygen-sensitive pathways. Itaconate blocks the enzyme called Sdh (succinate dehydrogenase), which not only ensures the functioning of the tricarboxylic acid cycle but also links the cycle to cellular respiration and signaling pathways.

Thus, itaconate acts on both functions of the Sdh enzyme, adjusting the cells' Krebs cycle and respiration. When the enzyme is blocked in macrophages, both processes become interrupted, and this impairs the cells' activation. "Noteworthy, itaconate acts as an anti-oxidant and anti-inflammatory agent," says Vicky Lampropoulou, the lead author of the paper and researcher at the laboratory of Maxim Artyomov at Washington University in St. Louis. "At the same time, itaconate is naturally produced by mammalian immune cells. These features make it attractive for use in adjuvant therapy for numerous diseases, in which excessive inflammation and oxidative stress associate with pathology, like heart ischemia, metabolic disorders and perhaps even autoimmunity."

The researchers have already demonstrated that they can use itaconate to reach the desired effect in living organisms. Experiments with mice have shown that the substance reduces damage after heart attack, acting by the same mechanism of locking the Sdh enzyme. However, according to the scientists, more work is needed to successfully apply the method to humans.

Media Contact

Dmitry Malkov
dvmalkov@corp.ifmo.ru
7-953-377-5508

 @spbifmo_en

http://en.ifmo.ru/ 

Dmitry Malkov | EurekAlert!

More articles from Health and Medicine:

nachricht Rabies viruses reveal wiring in transparent brains
19.01.2017 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Traffic jam in empty space

New success for Konstanz physicists in studying the quantum vacuum

An important step towards a completely new experimental access to quantum physics has been made at University of Konstanz. The team of scientists headed by...

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Sustainable Water use in Agriculture in Eastern Europe and Central Asia

19.01.2017 | Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

 
Latest News

New Study Will Help Find the Best Locations for Thermal Power Stations in Iceland

19.01.2017 | Earth Sciences

Not of Divided Mind

19.01.2017 | Life Sciences

Molecule flash mob

19.01.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>