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.

Therapeutic Properties of Bioactive Compounds from Different Honeybee Products

“…A mechanism putatively linked to 10-HDA anti-inflammatory effect is the inhibition of LPS-induced NF-κB activation observed in the murine macrophage cell line RAW264 (Sugiyama et al, 2012). …”

Study of the Royal Jelly Free Fatty Acids by Liquid Chromatography-High Resolution Mass Spectrometry (LC-HRMS)

“…As described in the introduction, the unusual free fatty acids of RJ have been shown to exhibit a variety of bioactivities such as antimicrobial, anti-inflammatory, immunomodulatory, and growth promoting activities [5][6][7][8][9][10][11]. However, no attention has been paid so far on the potential interactions of RJ fatty acids with free fatty acid receptors.…”

“…Watanabe et al showed that the major specific hydroxy fatty acids (10-HDA and 10-hydroxydecanoic acid) of RJ activate transient receptor potential ankyrin 1 (TRPA1) receptor and such an activation induces thermogenesis and energy expenditure [6]. 10-HDA was found to inhibit LPS-induced IL-6 production and NF-κB activation in a dose-dependent manner [7], and to exert immunomodulatory effects on human monocyte-derived dendritic cells [8]. More recently, the in vitro anti-inflammatory effects of these RJ fatty acids as well as sebacic acid (decanedioic acid) was evaluated and compared in lipopolysaccharide-stimulated RAW264.7 macrophages [9], while the bactericide and anti-inflammatory activity of 10-HDA in human colon cancer cells was studied [10].…”

Inhibitory effect of 10-hydroxydecanoic acid on lipopolysaccharide-induced nitric oxide production via translational downregulation of interferon regulatory factor-1 in RAW264 murine macrophages

“…Moreover, ω3-fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, are sources of resolvins, which exert potent anti-inflammatory and pro-resolving effects via inhibiting TLR signaling (1). Recently, we reported that 10-hydroxy-trans-2-decenoic acid (10H2DA), which is a principal lipid component of royal jelly, has inhibitory effects on lipopolysaccharide (LPS)-induced interleukin (IL)-6 and LPS-and interferon (IFN)-γ-induced nitric oxide (NO) production in murine macrophages (36,37,39). Royal jelly also contains 10-hydroxydecanoic acid (10HDA) at a high concentration (> 100 mM), which is almost same as that of 10H2DA.…”