Quercetin Attenuates MRGPRX2-Mediated Mast Cell Degranulation via the MyD88/IKK/NF-κB and PI3K/AKT/ Rac1/Cdc42...

Area of Science:

• Immunology
• Pharmacology

Background:

• CMRF35-like molecule-1 (CLM-1), a CD300 family receptor, inhibits MRGPRX2-mediated mast cell degranulation.
• Understanding CLM-1 agonists is crucial for developing treatments for allergic diseases.
• Quercetin, a plant-derived compound, is known to inhibit histamine release from immune cells.

Purpose of the Study:

• To investigate the inhibitory effects of quercetin on MRGPRX2-mediated mast cell degranulation through CLM-1 activation.

Main Methods:

• Utilized CLM-1-knockdown LAD2 cells to assess degranulation markers (β-hexosaminidase, histamine, Ca2+).
• Employed Surface Plasmon Resonance (SPR) and molecular docking to analyze quercetin-CLM-1 binding affinity and interactions.
• Investigated quercetin's effects on intracellular signaling pathways (SHP-1, MyD88/IKK/NF-κB, PI3K/AKT/Rac1/Cdc42) and MRGPRX2 receptor expression.

Main Results:

• C48/80 stimulation increased degranulation markers in CLM-1-knockdown cells.
• Quercetin exhibited high-affinity binding to CLM-1 (KD = 2.962×10-5 mol/L) via hydrogen bonds.
• Quercetin selectively activated CLM-1, inhibiting downstream signaling and leading to MRGPRX2 receptor internalization.

Conclusions:

• Quercetin functions as a CLM-1 agonist, effectively inhibiting MRGPRX2-mediated mast cell degranulation.
• Quercetin demonstrates potential as a therapeutic agent for allergic diseases.