A phytosterol derivative, 3-O-beta-D-glucopyanosylspinasterol (spinasterol-Glc) isolated from leaves of Stewartia koreana was reported to inhibit LPS-induced cytokine production in macrophage cells. Thymus and activation regulated chemokine (TARC/CCL17) is produced in response to pro-inflammatory cytokines in keratinocytes, which is implicated in the development of inflammatory skin diseases. In present study, we investigated the effect of spinasterol-Glc on production of TARC/CCL17 induced by TNF-alpha and IFN-gamma in human HaCaT keratinocytes. Spinasterol-Glc inhibited the mRNA and protein expression of TARC/CCL17 induced by TNF-alpha/IFN-gamma in a dose-dependent manner. Inhibitors of c-Raf-1, p38 MARK, and JAK2, suppressed the TNF-alpha/IFN-gamma-induced production of TARC/CCL17, and phosphorylation of these signaling molecules were attenuated by spinasterol-Glc. The compound also inhibited phosphorylation of IKK alpha/beta and I kappa B-alpha, and reduced translocation of NF-kappa B to the nucleus. We demonstrated that spinasterol-Glc suppressed the NF-kappa B-driven and the GAS-driven expression of luciferase reporter gene induced by TNF-alpha and IFN-gamma. In addition, spinasterol-Glc inhibited the DNA binding of NF-kappa B and STAT1 to its cognate binding site. These results suggest that spinasterol-Glc has effective inhibitory effects on production of TARC/CCL17 in keratinocytes via inhibition of NF-kappa B as well as STAT activation, and could be utilized for development of a potential therapeutic agent against skin inflammatory diseases. (C) 2012 Elsevier Inc. All rights reserved.