Modulation of Mast Cell Activation via MRGPRX2 by Natural Oat Extract

The Mas-related G protein-coupled receptor (MRGPR) X2 is expressed on skin mast cells and can be stimulated by an unusually broad spectrum of ligands, including specific drugs and even endogenous peptides. MRGPRX2 activation can induce mast cell degranulation and consequently mediator release, leading to inflammatory and hypersensitivity reactions. In addition, MRGPRX2 mediates pain and itching sensations, leading to increased efforts to identify MRGPRX2 inhibitors, including plant-derived compounds. Components within oat extracts have been shown to mediate anti-inflammatory and itch-relieving properties, but a possible inhibitory effect on MRGPRX2 activation has not yet been investigated. We aimed to fill this gap and explored whether an oat kernel extract can modulate MRGPRX2 activation. For this purpose, we established a mast cell model with the human LAD2 cell line and used it to investigate the consequences of exposure to oat extract. While we did not observe any influence on cell viability, we analyzed the impact of oat extract on MRGPRX2-mediated mast cell activation and degranulation initiated by the three confirmed MRGPRX2 ligands c48/80, substance P, and cortistatin 14. Exposure to oat extract resulted in a significant reduction in mast cell degranulation for all three ligands, as assessed by the release of β-hexosaminidase, tryptase, cell surface expression of CD63 and CD107a, and phosphorylation of ERK. All results were confirmed with primary human mast cells. Thus, we demonstrated for the first time that oat extract leads to a significant reduction in MRGPRX2 activation, pointing to a previously unrecognized capacity of natural compounds to modulate this pathway.