Mycoepoxydiene inhibits antigen-stimulated activation of mast cells and suppresses IgE-mediated anaphylaxis in mice
Mycoepoxydiene inhibits antigen-stimulated activation of mast cells and suppresses IgE-mediated anaphylaxis in mice
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Mycoepoxydiene 抑制小鼠中抗原刺激的肥大细胞活化并抑制 IgE 介导的过敏反应
DOI：
10.1016/j.intimp.2013.06.029
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发表时间：
2013-10-01
影响因子：
5.6
通讯作者：
Yu, Chun-dong
中科院分区：
文献类型：
--
作者：
Xia, Xiao-chun;Chen, Qiang;Yu, Chun-dong
霉环氧二烯(MED)是从一种与红树林相关的海洋真菌中分离得到的聚酮类化合物。已有研究表明，MED具有抗癌、抗炎等多种作用。然而，它对过敏反应的影响仍不清楚。肥大细胞在IgE介导的变态反应中起着关键作用。高亲和力的IgE受体(Fc Epsilon RI)聚集在肥大细胞表面，激活一系列信号事件，导致肥大细胞脱颗粒和细胞因子的产生。我们的研究表明，MED可以显著抑制抗原刺激的肥大细胞脱颗粒和细胞因子的产生，以及IgE介导的被动皮肤过敏反应(PCA)。此外，我们还发现MED抑制抗原诱导的Syk的激活，进而抑制肥大细胞中PLC-Gamma 1、Akt和MAPKs的磷酸化，如细胞外信号调节激酶(ERK)、c-jun氨基末端激酶(JNK)和p38。总之，我们的研究表明MED可以抑制肥大细胞的激活，并通过抑制Syk的激活来保护小鼠免受肥大细胞介导的过敏反应的影响。这些结果表明，MED是一种潜在的化合物，可以开发出一种有前途的抗过敏药物。(C)2013爱思唯尔B.V.保留所有权利。
Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus associated with mangrove forest. It has been shown that MED has many kinds of effects such as anti-cancer and anti-inflammatory activities. However, its effects on anaphylaxis are still unknown. Mast cells play a pivotal role in IgE-mediated allergic response. Aggregation of the high affinity IgE receptor (Fc epsilon RI) on the surface of mast cell activates a cascade of signaling events leading to the degranulation and cytokine production in mast cells. Our study showed that MED could significantly suppress antigen-stimulated degranulation and cytokine production in mast cells and IgE-mediated passive cutaneous anaphylaxis (PCA) in mice. Furthermore, we found that MED suppressed antigen-induced activation of Syk, and subsequently inhibited the phosphorylation of PLC gamma 1, Akt, and MAPKs such as extracellular signal-regulated kinase (ERK), c-jun N-terminal kinase (JNK), and p38 in mast cells. Collectively, our study demonstrates that MED can inhibit the activation of mast cells and protect mice from mast cell-mediated allergic response through inhibiting the activation of Syk. These results suggest that MED is a potential compound for developing a promising anti-anaphylaxis drug. (C) 2013 Elsevier B.V. All rights reserved.