title: Mycoepoxydiene inhibits antigen-stimulated activation of mast cells and suppresses IgE-mediated anaphylaxis in mice.
abstract: 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.
authors.affiliation: School of Life Sciences, Xiamen University, Xiamen, China.
authors.forename: Xiao-chun
authors.initials: XC
authors.lastname: Xia
authors.forename: Qiang
authors.initials: Q
authors.lastname: Chen
authors.forename: Kun
authors.initials: K
authors.lastname: Liu
authors.forename: Ping-li
authors.initials: PL
authors.lastname: Mo
authors.forename: Jing-wei
authors.initials: JW
authors.lastname: Zhu
authors.forename: Ming-qiang
authors.initials: MQ
authors.lastname: Zhuang
authors.forename: Yue-mao
authors.initials: YM
authors.lastname: Shen
authors.forename: Chun-dong
authors.initials: CD
authors.lastname: Yu
mesh_terms: D000707:Anaphylaxis / Q000188:drug therapy* / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology; D001952:Bridged-Ring Compounds / Q000378:metabolism* / Q000494:pharmacology; D015550:Cell Degranulation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D005658:Fungi / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011753:Pyrones / Q000378:metabolism* / Q000494:pharmacology; D000072377:Syk Kinase
chemical_list: D000941:Antigens; D001952:Bridged-Ring Compounds; D047908:Intracellular Signaling Peptides and Proteins; D011753:Pyrones; C476085:mycoepoxydiene; D007073:Immunoglobulin E; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse
keywords: IgE; Mast cell; Mycoepoxydiene; Passive cutaneous anaphylaxis; Syk