Inhibition of interferon-γ-induced nitric oxide production by 10-hydroxy-trans-2-decenoic acid through inhibition of interferon regulatory factor-8 induction.

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.