Estudios científicos
Resveratrol inhibits MRGPRX2-mediated mast cell activation via Nrf2 pathway.
Abstract:
Mast cells (MCs) are crucial effectors in inflammation and allergic reactions. The Mas-related G-protein-coupled receptor X2 (MRGPRX2) was the MC-specific receptor and play a key role in IgE-independent allergic reactions. The activation of the Nuclear factor erythroid derived 2-related factor 2 (Nrf2) is involved in IgE-mediated MC degranulation. Resveratrol (Res) is a polyphenolic compound in red wine and has been reported to exert a variety of pharmacological effects. In the current study, we investigated the effect of Res in regulating MRGPRX2-mediated MC activation and its underlyingmechanism. We demonstrated that Res reduced compound 48/80 (C48/80)-induced calcium flux in MCs and inhibited MCs degranulation in vitro. Res also suppressed C48/80-induced hind paw extravasation, active systemic anaphylaxis, and MCs degranulation in mouse models of pseudo-allergy in vivo. Furthermore, PCR and immunohistochemistry assay suggest that Res up-regulates Nrf2 expression and Nrf2 inhibitor attenuates the protective effects of Res. In conclusion, Res exerts an inhibitory effect on MRGPRX2-mediated MCs activation by targeting Nrf2 pathway and may present a promising new therapeutic agent for the treatment of MRGPRX2-dependent anaphylactoid reactions.
Comentarios divulgativos:
Los mastocitos son células que tienen una función clave en la inflamación y las reacciones alérgicas. El receptor X2 acoplado a proteína G relacionado con Mas, es un receptor específico de los mastocitos, que participa en las reacciones alérgicas independientes de anticuerpos IgE. Este artículo tiene como objetivo investigar el papel del resveratrol en la regulación de la activación de mastocitos mediada por el receptor X2 y su mecanismo subyacente.
En un modelo de ratón pseudoalérgico, se observó que el resveratrol puede inhibir la activación de mastocitos mediada por este receptor X2. Estos resultados sugieren que el resveratrol podría ser un nuevo agente terapéutico útil en el tratamiento de las reacciones alérgicas inducidas por fármacos y enfermedades alérgicas dependientes de mastocitos.
