Mycoepoxydiene inhibits antigen-stimulated activation of mast cells and suppresses IgE-mediated anaphylaxis in mice

• Published in: International immunopharmacology 2013-10, Vol.17 (2), p.336-341
• Main Authors: Xia, Xiao-chun, Chen, Qiang, Liu, Kun, Mo, Ping-li, Zhu, Jing-wei, Zhuang, Ming-qiang, Shen, Yue-mao, Yu, Chun-dong
• Format: Article
• Language: English
• Subjects: Anaphylaxis - drug therapy; Anaphylaxis - immunology; Animals; Antigens - immunology; Bridged-Ring Compounds - metabolism; Bridged-Ring Compounds - pharmacology; Cell Degranulation - drug effects; Cells, Cultured; Female; Fungi - immunology; IgE; Immunoglobulin E - blood; Intracellular Signaling Peptides and Proteins - metabolism; MAP Kinase Signaling System - drug effects; Mast cell; Mast Cells - drug effects; Mast Cells - immunology; Mice; Mice, Inbred BALB C; Mycoepoxydiene; Passive cutaneous anaphylaxis; Phosphorylation - drug effects; Protein-Tyrosine Kinases - metabolism; Pyrones - metabolism; Pyrones - pharmacology; Syk; Syk Kinase
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/j.intimp.2013.06.029

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 (FcεRI) 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 PLCγ1, 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. •Mycoepoxydiene (MED) is a polyketide isolated from a marine fungus.•MED inhibits degranulation and cytokine production in activated mast cells.•MED suppresses IgE-mediated passive cutaneous anaphylaxis (PCA) in mice.•MED suppresses mast cell activation and PCA through blocking Syk activation.