Spinasterol‐glucose inhibits IFN‐γ/TNF‐α‐induced expression of TARC/CCL17 via blocking NF‐κB and STAT1 activation in human HaCaT keratinocytes

Abstract

TARC/CCL17 is a Th2‐type chemokine and is implicated in the development of Th2‐skewed allergic diseases. TARC/CCL17 expression is induced by pro‐inflammatory cytokines such as IFN‐γ and TNF‐α. A phytosterol, 3‐O‐β‐D‐glucopyanosylspinasterol (spinasterol‐Glc), was isolated from Stewartia koreana leaves, and was previously shown to inhibit the production of NO and pro‐inflammatory cytokines in macrophage cells. In the present study, we investigated the effect of Spinasterol‐Glc on production of TARC/CCL17 induced by IFN‐γ and TNF‐α in HaCaT keratinocytes. Pretreatment of HaCaT cells with spinasterol‐Glc inhibited the mRNA and protein expression of TARC/CCL17 induced by IFN‐γ/TNF‐α in a dose‐dependent manner. Spinasterol‐ Glc suppressed IFN‐γ/TNF‐α‐induced activation of NF‐κB and STAT1. Spinastrol‐Glc also inhibited phosphorylation of IκB‐α and IKKα/β as well as nuclear translocation of NF‐κB. We demonstrated that spinasterol‐Glc reduced IFN‐γ/TNF‐α‐induced transcription of the NF‐κB‐ and the GAS‐ minimal promoters. In addition, spinasterl‐Glc suppressed the DNA binding of NF‐κB and STAT1 to its cognate consensus site. These results suggest that spinasterol‐Glc has effective inhibitory effects on production of TARC/CCL17 via inhibition of NF‐κB as well as STAT activation, and may be used as a potential anti‐inflammatory agent for the prevention and treatment of skin inflammatory diseases.