Researchers from the University of Murcia reveal one of the mechanisms involved in allergic processes
It is known that between 20% and 25% of the world’s population suffers from some type of allergy, that is, almost one in four people. Many people, if one takes into account that until now the exact mechanism by which some of the allergies are generated is not yet known. Of course, there are numerous studies carried out on allergy and its mechanisms of action, and with this knowledge, the drugs that are currently available have been developed, but the molecular process by which pro-inflammatory substances (such as histamine) are released into the space that surrounds the other cells and gives rise to the more well-known symptoms (inflammation, rhinitis, itching, rashes, asthma, etc.) still remains to be fully understood by science.
In trying to unveil this interesting secret of nature, the Biomembranes group of the University of Murcia works, which is also part of the Murcian Institute of Biosanitary Research (IMIB). Specifically, David López Martínez and Emilio M. Serrano, predoctoral hired by the Ministry of Universities and the University of Murcia, in collaboration with Antonio Luis Egea, postdoctoral hired at the Marseille Cancer Research Center, and under the direction of the Professors Senena Corbalán and Juan Carmelo Gómez.
Like almost everything that revolves around biology, it is a very complex process. Large amounts of protein are involved and there are still many steps of it that remain undiscovered. David López explains it with a metaphor: “If proteins were the workers in a chain of information transmission of a message, we need to know how each of these workers works and how they transmit that message from one to the other. If something goes wrong in any of these points, we all understand that the message will arrive in the wrong way to its recipient or may not even arrive (at that moment the allergic reaction is generated). In the same way, if we know all the details of that chain of transmission, we can act to make modifications that speed up or slow down the communication process, acting through the design of new drugs (preventing said reaction from occurring) ».
“If proteins were workers in a chain of information transmission of a message, we need to know how each of these workers works and how they transmit that message from one to the other”
For a long time, the UMU group has focused on studying a family of proteins called PKC, which are found inside cells and are essential for their proper functioning. Now, the researchers sought to determine the exact region of one of these proteins (PKC epsilon), which interacts with a lipid located in the plasma membrane of cells (the layer that is around it) and which is called ‘phosphatidic acid. ‘, since they are involved in allergic processes. “The membrane is the outer part made up of lipids, which surrounds and defines the cell. Under normal conditions, the amounts of phosphatidic acid are low and, when an allergic process is triggered, this lipid increases in the membrane ”, says López.
David López Martínez and Emilio M. Serrano, predoctoral recruits, at the University of Murcia. /
In fact, researchers have observed how, after the interaction of PKC epsilon with phosphatidic acid, the release of pro-inflammatory substances responsible for the allergic process is favored thanks to the action of PKC epsilon on another protein located in the membrane and that is called SNAP23.
New treatments
Obviously, it has not been by chance that the UMU team has reached these conclusions, being able to detect which elements interact with each other and generate the aforementioned effects. In the Biomembranes laboratory, different proteins that interact with membrane lipids and the function they perform are studied. Emilio M. Serrano points out that, “in a first phase, a bioinformatic study was carried out to predict the 3D structure of this protein (PKC epsilon) and find out the region that could be involved in membrane binding. The work of Antonio Luis Egea during his doctoral thesis consisted of experimentally confirming the different bioinformatic hypotheses to describe the way in which this protein recognizes the phosphatidic acid present in the membrane, determining which region is involved ».
Subsequently, David López and Emilio M. Serrano have worked to discover the consequences that this recognition could have on the part of PKC epsilon and the effect that it would trigger after its union in the membrane. “To do this – they indicate – we decided to use cells similar to mast cells, which are model cells to study allergic processes. After a lot of work studying different proteins, we discovered that he was modifying a protein called SNAP23 and that this could favor the release of the contents of the granules of these cells that contain histamine and other substances with a powerful inflammatory activity.
Their findings provide the scientific community with the knowledge of another step in the cellular signaling chain of the proteins they have studied.
«Based on this knowledge, it is possible to continue discovering the successive steps that occur in this complex mechanism, and also use this information for an application to design drugs or therapies that block this step in the chain that produces a greater release of pro-inflammatory substances such as histamine ”, explains Emilio M. Serrano.
Currently, the drugs that are used to treat allergy what they do is block these pro-inflammatory substances released by the cells (specifically histamine, hence its name, antihistamine). However, acting in a step before the chain and preventing these substances from being released, a new therapy could be designed to treat and regulate allergies, an ailment that, today, is increasing exponentially in the population .
Another good news is that, although there may be different factors that affect the allergic process, these steps could be shared in different reactions, even though their origin is different. The different exacerbated or milder responses depend on a wide variety of factors, generating different symptoms. However, in the words of López: «In our research, we have taken as a model a cell line already established by the scientific community that is used as an allergy model, given that it has receptors for IgE antibodies, which are normally found in small amounts. in the blood, but a high level of this type of antibody can be a sign of a disproportionate reaction of the body to certain allergens. By experimentally adding IgE and its corresponding antigen, pro-inflammatory substances are released, thus allowing the characterization of the process ”.
To carry out their work, the researchers have had funding from the Ministry of Science and Innovation and the Seneca Foundation. As well as the Ministry of Universities and the University of Murcia. In addition, they have collaborated with the Marseille Cancer Research Center and the Barcelona Institute of Molecular Biology, among others.
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