title: Inhibitory effect of 10-hydroxy-trans-2-decenoic acid on LPS-induced IL-6 production via reducing IκB-ζ expression.
abstract: The effect of 10-hydroxy-trans-2-decenoic acid (10H2DA), a major fatty acid component of royal jelly, was investigated on LPS-induced cytokine production in murine macrophage cell line, RAW264 cells. 10H2DA inhibited LPS-induced IL-6 production dose-dependently, but did not inhibit TNF-α production. 10H2DA inhibited LPS-induced NF-κB activation in a dose-dependent fashion. In addition, NF-κB activation induced by over-expression of either MyD88 or Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF) was also inhibited by 10H2DA. Degradation of IκB-α and phosphorylation of IκB kinase-α were not inhibited by 10H2DA. On the other hand, reduction of LPS-induced IκB-ζ expression was discovered. Production of lipocalin-2 and granulocyte colony-stimulating factor (G-CSF), which is dependent on IκB-ζ, was also inhibited by 10H2DA, whereas that of IκB-ζ-independent cytokines/chemokines, such as IFN-β, murine monocyte chemotactic protein-1 (JE), macrophage inflammatory protein (MIP)-1α and MIP-2, was not. Together, 10H2DA specifically inhibited LPS-induced IκB-ζ expression, followed by inhibition of IκB-ζ-dependent gene production. These results suggest that 10H2DA is one of the components of royal jelly to show anti-inflammatory effects and could be a therapeutic drug candidate for inflammatory and autoimmune diseases associated with IκB-ζ and IL-6 production.
authors.affiliation: Department of Biopharmaceutical Sciences, Laboratory of Microbiology, Gifu Pharmaceutical University, Gifu, Japan. sugiyama@gifu-pu.ac.jp
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Keita
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shunji
authors.initials: S
authors.lastname: Tokoro
authors.forename: Takaki
authors.initials: T
authors.lastname: Gotou
authors.forename: Paola
authors.initials: P
authors.lastname: Neri
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mori
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation; D005227:Fatty Acids / Q000737:chemistry; D005229:Fatty Acids, Monounsaturated / Q000737:chemistry / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism; D051550:I-kappa B Kinase / Q000235:genetics / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D000071068:Lipocalin-2; D054834:Lipocalins / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D000099219:Royal Jelly
chemical_list: D000209:Acute-Phase Proteins; D000893:Anti-Inflammatory Agents; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D016179:Granulocyte Colony-Stimulating Factor; D051550:I-kappa B Kinase; D015850:Interleukin-6; D000071068:Lipocalin-2; D054834:Lipocalins; D008070:Lipopolysaccharides; D015513:Oncogene Proteins; D000099219:Royal Jelly; C071332:Lcn2 protein, mouse; C055543:10-hydroxy-2-decenoic acid