RAW 264.7細胞におけるLPSで誘導される誘導型NO合成酵素の発現に対するCaffeic Acid Undecyl Esterの阻害について

We synthesized caffeic acid undecyl ester (CAUE),and found that it exhibited strong inhibitory effect of lipopolysaccharide (LPS) -induced nitric oxide (NO) production in murine macrophage-like RAW 264.7 cells.We examined the effect of CAUE on the expression inducible nitric oxide synthase (iNOS) in LPS-stimulated RAW 264.7 cells.Western blot analysis performed with specific anti-iNOS antibody showed that a decrease in NO was accompanied by a decrease in the level of iNOS protein with dose-dependent manner (CAUE:0.1～1.0μM).To clarify the mechanistic basis for CAUE\u27s ability to inhibit the induction of iNOS,we examined the effect of CAUE on nuclear factor (NF)-κB,Inhibitor-κB (IκB) degradation and phosphorylation of extracellular-signaling regulated Kinases,ERK 1/2.CAUE potently suppressed the transcriptional activity of NF-κB,IκB degradation and activation of ERK.Since NF-κB was activated by following IκBα degradation,the recovery of IκBα protein indicating that CAUE inhibited the activation of degradation following NF-κB.These finding suggest that CAUE has the inhibitory effect on LPS-induced NO production and expression of iNOS in macrophage by the inhibition of IκB degradation and NF-κB activation,which may be mediated through blockage in the phospholylation ERK