title: Saucerneol F inhibits tumor necrosis factor-α and IL-6 production by suppressing Fyn-mediated pathways in FcεRI-mediated mast cells.
abstract: 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.
authors.affiliation: College of Pharmacy, Yeungnam University, Gyeongsan 712-749, Republic of Korea.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Donggen
authors.initials: D
authors.lastname: Piao
authors.forename: Haiyan
authors.initials: H
authors.lastname: Zhang
authors.forename: Xian
authors.initials: X
authors.lastname: Li
authors.forename: Guang Hsuan
authors.initials: GH
authors.lastname: Chao
authors.forename: Soon Jin
authors.initials: SJ
authors.lastname: Park
authors.forename: Young-Chae
authors.initials: YC
authors.lastname: Chang
authors.forename: Cheorl-Ho
authors.initials: CH
authors.lastname: Kim
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.forename: Seung-Hyun
authors.initials: SH
authors.lastname: Jung
authors.forename: Jung-Hye
authors.initials: JH
authors.lastname: Choi
authors.forename: Jong Keun
authors.initials: JK
authors.lastname: Son
authors.forename: Hyeun Wook
authors.initials: HW
authors.lastname: Chang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D017705:Lignans / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010766:Phosphorylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051076:Proto-Oncogene Proteins c-fyn / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017455:Receptors, IgE / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000093242:Interleukin-6 Inhibitors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D015850:Interleukin-6; D017705:Lignans; D051076:Proto-Oncogene Proteins c-fyn; D017455:Receptors, IgE; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C498144:Rela protein, mouse; C577686:interleukin-6, mouse; C572382:saucerneol F; C494960:Fyn protein, mouse
keywords: Fyn; Mouse bone marrow-derived mast cells; Proinflammatory cytokine; Saucerneol F; Syk; Transcriptional factor