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Sauchinone suppresses FcεRI-mediated mast cell signaling and anaphylaxis through regulation of LKB1/AMPK axis and SHP-1-Syk signaling module

2019; Elsevier BV; Volume: 74; Linguagem: Inglês

10.1016/j.intimp.2019.105702

1878-1705

Yifeng Deng, Fansi Jin, Xian Li, Sung Joon Park, Jae‐Hoon Chang, Dong Young Kim, Jung‐Ae Kim, Joo‐Won Nam, Hyukjae Choi, Youn Ju Lee, Hyeun Wook Chang,

Hops Chemistry and Applications

Sauchinone, the biologically active lignan of Saururus chinensis, has been reported to have anti-inflammatory, antitumor, antioxidant, and hepatoprotective properties. However, little is known about the effect of sauchinone on FcεRI-mediated mast cell activation. The aim of this study was to evaluate the anti-allergic activity of sauchinone and the underlying mechanism using mouse bone marrow-derived mast cells (BMMCs) and the mast cell-mediated passive cutaneous anaphylaxis (PCA) model. Sauchinone markedly suppressed FcεRI-mediated activation of positive signaling mediators, including Syk, linker for activation of T cells (LAT), phospholipase C (PLC)γ, mitogen-activated protein (MAP) kinases, Akt, IκB kinase (IKK), and intracellular Ca2+, and increased the activation of negative signaling mediators, including liver kinase B (LKB)1/AMP-activated protein kinase (AMPK) and Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1. Interestingly, sauchinone increased the interaction between SHP-1 and Syk. Consequently, sauchinone significantly suppressed FcεRI-mediated BMMC degranulation and synthesis of eicosanoids and cytokines. These inhibitory effects of sauchinone were diminished in BMMCs treated with siRNAs targeting LKB1, AMPKα2, or SHP-1, and in BMMCs isolated from AMPKα2-deficient mice. In addition, administration of sauchinone markedly suppressed the IgE-mediated PCA reaction in wild-type mice, and this inhibitory effect was significantly reduced in AMPKα2-/- mice. Taken together, these data suggest that sauchinone suppresses FcεRI-mediated mast cell activation and anaphylaxis through modulation of the LKB1/AMPK and SHP-1/Syk pathways. Therefore, sauchinone might be a potential therapeutic agent for the treatment of allergic inflammatory diseases.