title: Inhibition of interferon-γ-induced nitric oxide production by 10-hydroxy-trans-2-decenoic acid through inhibition of interferon regulatory factor-8 induction.
abstract: 10-Hydroxy-trans-2-decenoic acid (10H2DA) is a major lipid component of royal jelly, a honey bee secretion used to nourish the queen bee and young larvae. In this study, we examined the effect of 10H2DA on interferon (IFN)-γ-induced nitric oxide (NO) production. IFN-γ-induced NO production and activation of the inducible NO synthase promoter were significantly inhibited by 10H2DA. IFN-γ-induced phosphorylation of signal transducer and activator of transcription-1 was not affected by 10H2DA. In contrast, IFN-γ-induced tumor necrosis factor (TNF)-α production and nuclear factor (NF)-κB activation were inhibited by 10H2DA. IFN-γ-mediated induction of interferon regulatory factor (IRF)-8, but not IRF-1, was also inhibited by 10H2DA. IFN-γ-induced TNF-α production followed by activation of NF-κB is known to be essential for NO production. Together, 10H2DA inhibited IFN-γ-induced NO production by inhibiting IRF-8 induction and TNF-α production. 10H2DA might modulate IFN-γ-mediated cellular responses by inhibiting the induction of IRF-8 and IRF-8-dependent genes.
authors.affiliation: Department of Biopharmaceutical Sciences, Laboratory of Microbiology, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Keita
authors.initials: K
authors.lastname: Takahashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Shunji
authors.initials: S
authors.lastname: Tokoro
authors.forename: Paola
authors.initials: P
authors.lastname: Neri
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
mesh_terms: D000818:Animals; D002460:Cell Line; D004789:Enzyme Activation / Q000276:immunology; D005227:Fatty Acids / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D050835:Interferon Regulatory Factors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000276:immunology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000276:immunology; D014158:Transcription, Genetic / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D000099219:Royal Jelly; D000099185:Interferon Regulatory Factor-8
chemical_list: D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D050835:Interferon Regulatory Factors; D007371:Interferon-gamma; D016328:NF-kappa B; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D000099219:Royal Jelly; D000099185:Interferon Regulatory Factor-8; C494080:Stat1 protein, mouse; C052476:2-decenoic acid