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: Xiao-chun Xia, Qiang Chen, Kun Liu, Ping-li Mo, Jing-wei Zhu, Ming-qiang Zhuang, Yue-mao Shen, Chun-dong Yu
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 17 Issue 2 Pg. 336-41 (Oct 2013) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 23859869 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2013.

Chemical References

• Antigens
• Bridged-Ring Compounds
• Intracellular Signaling Peptides and Proteins
• Pyrones
• mycoepoxydiene
• Immunoglobulin E
• Protein-Tyrosine Kinases
• Syk Kinase
• Syk protein, mouse

Topics

• Anaphylaxis (drug therapy, immunology)
• Animals
• Antigens (immunology)
• Bridged-Ring Compounds (metabolism, pharmacology)
• Cell Degranulation (drug effects)
• Cells, Cultured
• Female
• Fungi (immunology)
• Immunoglobulin E (blood)
• Intracellular Signaling Peptides and Proteins (metabolism)
• MAP Kinase Signaling System (drug effects)
• Mast Cells (drug effects, immunology)
• Mice
• Mice, Inbred BALB C
• Phosphorylation (drug effects)
• Protein-Tyrosine Kinases (metabolism)
• Pyrones (metabolism, pharmacology)
• Syk Kinase