TY - JOUR
T1 - Salicylic acid inhibits Mas-related G protein-coupled receptor X2-mediated mast cell 2 activation and mitigates cutaneous pseudo-allergic reactions
AU - Zhou, Hongmei
AU - Zhao, Xi
AU - Ye, Dan
AU - Zhao, Qiang
AU - Yang, Mengyao
AU - Wang, Zhaoyang
AU - Wang, Li
AU - wang, Chao
AU - Geng, Songmei
AU - Zeng, Weihui
AU - Wang, Zhao
N1 - Publisher Copyright:
© 2025 Elsevier B.V.
PY - 2025/11/5
Y1 - 2025/11/5
N2 - Background: Pseudo-allergic reactions mediated by non-IgE mast cells (MCs) activation contribute to various dermatological conditions, with Mas-related G protein-coupled receptor X2 (MRGPRX2) recognized as a key receptor. Salicylic acid (SA) has long been applied in dermatology as a peeling agent with anti-inflammatory properties, but its role in MRGPRX2-associated pseudo-allergic responses remains unclear. Methods: In vivo, a murine skin pseudo-allergic reaction model combined with Evans blue dye extravasation assay was employed in C57BL/6 mice. In vitro, human skin-derived MCs and LAD2 cells were activated with MRGPRX2 agonists compound 48/80 (c48/80) and substance P (SP). Degranulation and calcium influx were assessed via β-hexosaminidase release and calcium influx assays. RT-qPCR quantified mRNA expression, while kinase phosphorylation and reactive oxygen species (ROS) levels were evaluated using western blotting and flow cytometry, respectively. MRGPRX2 cell surface expression was analyzed by flow cytometry and immunofluorescence. Results: In vivo, SA significantly reduced MRGPRX2-mediated skin edema and Evans blue dye extravasation. In vitro, SA inhibited MC degranulation and calcium influx in both human skin-derived MCs and LAD2 cells. It also suppressed the mRNA expression of inflammatory cytokines IL-4, IL-8, and TNF-α following MRGPRX2 activation. SA pre-treatment reduced ROS levels and inhibited extracellular signal-regulated kinase (ERK) phosphorylation. Additionally, prolonged SA exposure downregulated both MRGPRX2 mRNA and cell surface expression. Conclusions: SA demonstrates a dual-phase inhibitory effect on MRGPRX2-mediated pseudo-allergic reactions. Short-term SA treatment suppresses MC degranulation and cytokine production, whereas long-term treatment further reduces MRGPRX2 expression, highlighting the therapeutic potential of SA for MRGPRX2-associated dermatological disorders.
AB - Background: Pseudo-allergic reactions mediated by non-IgE mast cells (MCs) activation contribute to various dermatological conditions, with Mas-related G protein-coupled receptor X2 (MRGPRX2) recognized as a key receptor. Salicylic acid (SA) has long been applied in dermatology as a peeling agent with anti-inflammatory properties, but its role in MRGPRX2-associated pseudo-allergic responses remains unclear. Methods: In vivo, a murine skin pseudo-allergic reaction model combined with Evans blue dye extravasation assay was employed in C57BL/6 mice. In vitro, human skin-derived MCs and LAD2 cells were activated with MRGPRX2 agonists compound 48/80 (c48/80) and substance P (SP). Degranulation and calcium influx were assessed via β-hexosaminidase release and calcium influx assays. RT-qPCR quantified mRNA expression, while kinase phosphorylation and reactive oxygen species (ROS) levels were evaluated using western blotting and flow cytometry, respectively. MRGPRX2 cell surface expression was analyzed by flow cytometry and immunofluorescence. Results: In vivo, SA significantly reduced MRGPRX2-mediated skin edema and Evans blue dye extravasation. In vitro, SA inhibited MC degranulation and calcium influx in both human skin-derived MCs and LAD2 cells. It also suppressed the mRNA expression of inflammatory cytokines IL-4, IL-8, and TNF-α following MRGPRX2 activation. SA pre-treatment reduced ROS levels and inhibited extracellular signal-regulated kinase (ERK) phosphorylation. Additionally, prolonged SA exposure downregulated both MRGPRX2 mRNA and cell surface expression. Conclusions: SA demonstrates a dual-phase inhibitory effect on MRGPRX2-mediated pseudo-allergic reactions. Short-term SA treatment suppresses MC degranulation and cytokine production, whereas long-term treatment further reduces MRGPRX2 expression, highlighting the therapeutic potential of SA for MRGPRX2-associated dermatological disorders.
KW - MRGPRX2
KW - Mast cell
KW - Pseudo-allergy
KW - Salicylic acid
UR - https://www.scopus.com/pages/publications/105017313471
U2 - 10.1016/j.ejphar.2025.178189
DO - 10.1016/j.ejphar.2025.178189
M3 - 文章
C2 - 41005604
AN - SCOPUS:105017313471
SN - 0014-2999
VL - 1006
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
M1 - 178189
ER -