Journal of Inflammation Research (Oct 2024)
Quercetin Attenuates MRGPRX2-Mediated Mast Cell Degranulation via the MyD88/IKK/NF-κB and PI3K/AKT/ Rac1/Cdc42 Pathway
Abstract
Chenrui Zhao,1,2,* Yuanyuan Ding,2,* Yihan Huang,2 Chao Wang,2 Bin Guo,1 Tao Zhang2 1Department of Anesthesiology, Xi’an Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710054, People’s Republic of China; 2College of Pharmacy, Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bin Guo, Department of Anesthesiology, Xi’an Honghui Hospital, Xi’an Jiaotong University, Xi’an, 710054, People’s Republic of China, Email [email protected]: CMRF35-like molecule-1 (CLM-1) is a receptor of the CD300 family that inhibits MRGPRX2-mediated mast cell degranulation. Understanding the role and mechanism of CLM-1 agonist has significant implications for the treatment of allergic disease. Quercetin is a natural small molecule compound derived from plants and vegetables that has been shown to prevent histamine release by immune cells.Objective: This study aims to examine the inhibitory effects of quercetin on MRGPRX2-mediated mast cell degranulation via CLM-1.Results: We found that C48/80 stimulation resulted in significantly increased release of β-hexosaminidase, histamine and Ca2+ in CLM-1-knockdown LAD2 cells than in NC-LAD2 cells. Surface plasmon resonance (SPR) and molecular docking analyses revealed high-affinity binding between quercetin and CLM-1 (KD = 2.962× 10− 5 mol/L) mediated by the formation of hydrogen bonds. In addition, quercetin can selectively bind to CLM-1 on mast cells, leading to SHP-1 phosphorylation and subsequent inhibition of downstream MyD88/IKK/NF-κB signaling. Furthermore, activation of CLM-1 modulated the surface expression of MRGPRX2 by inhibiting F-actin, leading to internalization of the MRGPRX2 receptor via the PI3K/AKT/ Rac1/Cdc42 pathway.Conclusion: Quercetin is a promising treatment for allergic diseases by acting as a CLM-1 agonist that inhibits MRGPRX2-mediated mast cell degranulation. Keywords: quercetin, CLM-1, inhibition, MRGPRX2, mast cell degranulation
