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Int Immunopharmacol ; 17(2): 336-41, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23859869

RESUMO

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.


Assuntos
Anafilaxia/tratamento farmacológico , Hidrocarbonetos Aromáticos com Pontes/metabolismo , Fungos/imunologia , Mastócitos/efeitos dos fármacos , Pironas/metabolismo , Anafilaxia/imunologia , Animais , Antígenos/imunologia , Hidrocarbonetos Aromáticos com Pontes/farmacologia , Degranulação Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Imunoglobulina E/sangue , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mastócitos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Fosforilação/efeitos dos fármacos , Proteínas Tirosina Quinases/metabolismo , Pironas/farmacologia , Quinase Syk
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