Saucerneol F inhibits tumor necrosis factor-α and IL-6 production by suppressing Fyn-mediated pathways in FcεRI-mediated mast cells

The aim of this study was to investigate the effect of saucerneol F (SF) on the productions of the pro-inflammatory cytokines, TNF-α and IL-6, in IgE/Ag-induced mouse bone marrow-derived mast cells (BMMCs). SF dose-dependently suppressed the transcriptions of these pro-inflammatory cytokines. To identify the molecular mechanisms responsible for these suppressions, we examined the effect of SF on three important transcription factors; activator protein-1 (AP-1), nuclear factor-κB (NF-κB), and STAT5. It was found that SF inhibited the nuclear translocation of the p65 subunit of NF-κB to the nucleus and its DNA-binding ability. SF also attenuated mitogen-activated protein kinase (MAPK)-mediated AP-1 activation and STAT5 activation. Biochemical analysis of FcεRI-mediated signaling pathways demonstrated that SF inhibited the phosphorylation of Fyn and multiple downstream signaling processes, including Syk, Gab2, and the Akt/IKK/IκB and MAPK pathways. Taken together, our results suggest that SF inhibits the production of pro-inflammatory cytokines by suppressing Fyn kinase-dependent signaling events.