Here’s an interesting new finding in Mast Cell Inhibition mechanisms
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Dec 11, 2024
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A new way to treat inflammatory skin conditions: Experimental compound targets mast cells
In a mouse model of contact dermatitis, preventive application of a cream containing SYM2081 (right image) reduced skin swelling compared to placebo (left image). Credit: Youran Zhang
A new approach to treat rosacea and other inflammatory skin conditions could be on the horizon, according to a University of Pittsburgh study published in Science Translational Medicine.
The researchers found that a compound called SYM2081 inhibited inflammation-driving mast cells in mouse models and human skin samples, paving the way for new topical treatments to prevent itching, hives and other symptoms of skin conditions driven by mast cells.
“I’m really excited about the clinical possibilities of this research,” said senior author Daniel Kaplan, M.D., Ph.D., professor of dermatology and immunology at Pitt. “Currently, there aren’t a lot of good therapies that target mast cells, so we think that our approach could potentially have huge benefits in many skin conditions, including rosacea, eczema, urticaria and mastocytosis.”
Mast cells are filled with tiny packages, or granules, each brimming with histamine and other compounds that act as signals or activators of inflammatory pathways.
When mast cells are activated, the packages spill open, releasing compounds that trigger a suite of immune responses. This process, known as degranulation, is essential for protection against threats such as bee venom, snake bites and pathogenic bacteria, but erroneous activation of mast cells also triggers allergic reactions, including swelling, hives, itching and, in severe cases, anaphylaxis.
In a previous Cell
paper, Kaplan and his team found that neurons in the skin release a neurotransmitter called glutamate that suppresses mast cells. When they deleted these neurons or inhibited the receptor that recognizes glutamate, mast cells became hyperactive, leading to more inflammation.
“This finding led us to wonder if doing the opposite would have a beneficial effect,” said Kaplan. "If we activate the glutamate receptor
(Glutamate Receptor - latest research news and features),
maybe we can suppress mast cell activity and inflammation."
To test this hypothesis, lead author Youran Zhang, a medical student at Tsinghua University who did this research as a visiting scholar in Kaplan’s lab, and Tina Sumpter, Ph.D., a research assistant professor in the Pitt Department of Dermatology, looked at a compound called SYM2081, or 4-methylglutamate, that activates a glutamate receptor called GluK2 found almost exclusively on mast cells.
Sure enough, they found that SYM2081 effectively suppressed mast cell degranulation and proliferation in both mice and human skin samples. And when the mice received a topical cream containing SYM2081 before the induction of rosacea- or eczema-like symptoms, skin inflammation and other symptoms of disease were much milder.
According to Kaplan, these findings suggest that suppressing mast cells with a daily cream containing a GluK2-activating compound could be a promising way to prevent rosacea and other inflammatory skin conditions.