Quercetin Alleviates Chronic Urticaria by Negatively Regulating IgE-Mediated Mast Cell Activation Through CD300f

Area of Science:

• Immunology
• Dermatology
• Pharmacology

Background:

• Chronic urticaria (CU) is a prevalent skin condition driven by mast cell overactivation, often linked to immunoglobulin E (IgE)-mediated type I allergic reactions.
• Understanding the molecular mechanisms underlying CU is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the therapeutic efficacy of quercetin in a mouse model of ovalbumin (OVA)-induced chronic urticaria.
• To elucidate the molecular targets and mechanisms of quercetin's action in alleviating CU symptoms.

Main Methods:

• A chronic urticaria mouse model was established using ovalbumin (OVA) induction.
• Bioinformatic and multi-database analyses were employed to predict quercetin's molecular targets.
• Mast cell activation experiments, including CD300f knockdown, were conducted.
• Quantitative real-time PCR (RT-PCR) and Western blot assays were used to verify molecular mechanisms.

Main Results:

• Quercetin significantly reduced CU symptoms in mice, including wheal formation, scratching behavior, and eosinophilic infiltration.
• Quercetin inhibited the release of key inflammatory mediators such as IgE, histamine, TNF-α, MCP-1, and IL-13.
• Quercetin upregulated and activated CD300f, leading to downstream SHP-1 phosphorylation and inhibition of the AKT/IKK/NF-κB inflammatory pathway.
• Quercetin prevented IgE-mediated mast cell degranulation and F-actin cytoskeleton remodeling by binding to CD300f.

Conclusions:

• Quercetin demonstrates significant therapeutic potential for chronic urticaria by activating the CD300f/SHP-1 signaling pathway.
• Quercetin's mechanism involves inhibiting IgE-mediated mast cell degranulation and inflammatory responses via the AKT/IKK/NF-κB pathway.