Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction
Alisol B 23-Acetate Inhibits IgE/Ag-Mediated Mast Cell Activation and Allergic Reaction
复制标题
Alisol B 23-Acetate 抑制 IgE/Ag 介导的肥大细胞活化和过敏反应。
DOI：
10.3390/ijms19124092
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发表时间：
2018-12-01
影响因子：
5.6
通讯作者：
Kong, Dexin
中科院分区：
文献类型：
--
作者：
Shao, Chen;Fu, Bingjie;Kong, Dexin
泽泻醇B 23-乙酸酯（AB 23 A）是一种天然三萜类化合物，具有保肝和抗肿瘤活性。为了研究其抗炎活性，本研究检测了AB 23 A对肥大细胞和过敏反应的影响。AB 23 A抑制免疫球蛋白E/抗原（IgE/Ag）刺激的肥大细胞的脱颗粒，并且还以浓度依赖性方式减少白三烯C-4（LTC 4）的合成、白细胞介素-6（IL-6）的产生和环氧合酶-2（考克斯-2）的表达，而在骨髓来源的肥大细胞（BMMC）中没有显著的细胞毒性。AB 23 A抑制脾酪氨酸激酶（Syk）和下游信号分子，包括磷脂酶C（PLC）、丝氨酸-苏氨酸蛋白激酶/核因子κ-B激酶抑制剂/核因子κ-B（Akt/IKK/NF-B）和丝裂原活化蛋白激酶/胞质磷脂酶A（2）（MAPK/cPLA（2））。此外，AB 23 A阻断Ca 2+的动员。在其他肥大细胞系大鼠嗜碱性白血病（RBL）-2H3细胞和人肥大细胞系（HMC-1）中获得了类似的结果。此外，AB 23 A在急性过敏动物模型中减弱过敏反应，即被动皮肤过敏反应（PCA）。综上所述，本研究表明，AB 23 A抑制肥大细胞的活化，改善过敏反应，并可能成为治疗肥大细胞介导的过敏性疾病的先导化合物。
Alisol B 23-acetate (AB23A), a natural triterpenoid, has been reported to exert hepatoprotective and antitumor activities. Aiming to investigate the anti-inflammatory activity, this study examined the effect of AB23A on mast cells and allergic reaction. AB23A inhibited the degranulation of mast cells stimulated by immunoglobulin E/antigen (IgE/Ag), and also decreased the synthesis of leukotriene C-4 (LTC4), production of interlukin-6 (IL-6), and expression of cyclooxygenase-2 (COX-2) in a concentration-dependent manner with no significant cytotoxicity in bone marrow-derived mast cells (BMMCs). AB23A inhibited spleen tyrosine kinase (Syk) and the downstream signaling molecules including phospholipase C (PLC), serine-threonine protein kinase/inhibitor of nuclear factor kappa-B kinase/nuclear factor kappa-B (Akt/IKK/NF-B), and mitogen-activated protein kinases/cytosolic phospholipase A(2) (MAPK/cPLA(2)). Furthermore, AB23A blocked mobilization of Ca2+. Similar results were obtained in other mast cell lines Rat basophilic leukemia (RBL)-2H3 cells and a human mast cell line (HMC-1). In addition, AB23A attenuated allergic responses in an acute allergy animal model, passive cutaneous anaphylaxis (PCA). Taken together, this study suggests that AB23A inhibits the activation of mast cells and ameliorates allergic reaction, and may become a lead compound for the treatment of mast cell-mediated allergic diseases.