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

作者: Yue Lu , Donggen Piao , Haiyan Zhang , Xian Li , Guang Hsuan Chao

DOI: 10.1016/J.FCT.2013.06.056

关键词: GAB2Signal transductionProinflammatory cytokineChemistryFYNMAPK/ERK pathwayProtein kinase BCell biologySykIκB kinase

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

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