LB979 Mast cell activation via mas-related g protein-coupled receptor X2 is regulated by ryanodine-sensitive calcium stores

Mast cells (MCs) are tissue-resident immune cells, which play a pivotal role in skin hypersensitivity reactions. MCs activation via Mas-Related G Protein-Coupled Receptor X2 (MRGPRX2) is independent of the classical IgE-mediated pathway, gained much interest recently. Calcium mobilization crucial to mast cell and functional regulation. Ryanodine receptor (RYR) expresses on sarcoplasmic reticulum regulates intracellular calcium liberation. Although MRGPRX2 induces boosted levels, RYR mediated MC has not been fully addressed. We confirmed expression human skin-derived recognized most abundant RYR3 isoform. Human line (LAD2 cells) was utilized study triggered by agonists (c48/80 Substance P). pretreated with inhibitor (dantrolene) suppressed both release extracellular entry stimulated ligands. Degranulation assessed β-hexosaminidase likewise inhibited dantrolene. IL-13, IL-8 CCL-2 induction were at mRNA level when pre-treated inhibitor. The results demonstrate signaling, provide potential approach for MRGPRX2-mediated disorders.