College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
Food Chem Toxicol. 2013 Sep;59:696-702. doi: 10.1016/j.fct.2013.06.056. Epub 2013 Jul 11.
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.
本研究旨在探讨獐牙菜苦醇 F（SF）对 IgE/Ag 诱导的小鼠骨髓来源肥大细胞（BMMCs）中促炎细胞因子 TNF-α和 IL-6 产生的影响。SF 呈剂量依赖性抑制这些促炎细胞因子的转录。为了确定这些抑制作用的分子机制，我们研究了 SF 对三个重要转录因子；激活蛋白-1（AP-1）、核因子-κB（NF-κB）和 STAT5 的影响。结果发现，SF 抑制了 NF-κB 的 p65 亚基向核内的核易位及其 DNA 结合能力。SF 还减弱了丝裂原活化蛋白激酶（MAPK）介导的 AP-1 激活和 STAT5 激活。FcεRI 介导的信号通路的生化分析表明，SF 抑制了 Fyn 激酶依赖性信号事件，包括 Syk、Gab2 以及 Akt/IKK/IκB 和 MAPK 通路的磷酸化。综上所述，我们的结果表明，SF 通过抑制 Fyn 激酶依赖性信号事件抑制促炎细胞因子的产生。
