锡克
脱颗粒
免疫球蛋白E
肥大细胞
过敏反应
组胺
免疫学
过敏
过敏性炎症
化学
肿瘤坏死因子α
细胞因子
信号转导
药理学
生物
酪氨酸激酶
抗体
受体
生物化学
作者
Y. S. Lee,Sun Hur,T.‐Y. Kim
出处
期刊:Allergy
[Wiley]
日期:2014-01-22
卷期号:69 (4): 453-462
被引量:23
摘要
Mast cells play important roles in allergic inflammatory responses because they produce leukotrienes (LTs), prostaglandins (PGs), and a variety of inflammatory cytokines. Thus, pharmacological interventions for allergies have focused on inhibiting mast cell activation. Homoisoflavanone (HIF), isolated from Cremastra appendiculata Makino, has anti-angiogenic activities; however, its effects on allergic reactions have not been determined. The aim of this study was to assess the inhibitory effects of HIF on mast cell activation, which is critical for anti-allergic reaction and the underlying mechanisms.Enzyme-linked immunosorbent assays, quantitative real-time PCR, western blot analyses, and degranulation assay were performed to measure pro-inflammatory and allergic mediators in PMA/A23187- or IgE/antigen-stimulated mouse bone marrow-derived mast cells (BMMCs), HMC-1, RBL-1, or human PBMC-derived mast cells treated with or without HIF. The anti-allergic effects of HIF were determined in mouse models using dinitrophenol-immunoglobulin E-induced passive cutaneous anaphylaxis (PCA) and compound 48/80-induced ear swelling.Homoisoflavanone down-regulated PGD2 , LTB4 , and LTC4 production and inhibited the production of pro-inflammatory cytokines, such as interleukin-6 and tumor necrosis factor-α in PMA/A23187- or IgE/antigen-stimulated mast cells. The molecular mechanisms by which HIF caused these inhibitory effects were determined to be the inactivation of spleen tyrosine kinase (Syk) signaling and the concurrent suppression of cPLA2 . HIF inhibited IgE-mediated PCA and compound 48/80-induced ear swelling in mouse.Homoisoflavanone inhibited mast cell activation through the suppression of Syk pathway together with the inhibition of cPLA2 . Thus, it might be a good candidate molecule for allergic diseases.
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