A spinasterol glycoside repressed expression of the chemokine MDC/CCL22 induced by IFN-γ and TNF-α in human keratinocytes and inhibits DNCB-induced allergic skin inflammation (LB545)

The chemokine MDC/CCL22 is considered to be a pivotal mediator in the inflammatory responses during the development of inflammatory skin diseases, such as atopic dermatitis (AD). Expression of MDC/CCL22 gene can be induced by IFN-γ and TNF-α in keratinocytes, one of major cell types in the skin. In the present study, we investigated the effects of spinasterol-Glucose, one of phytosterols from Stewartia koreana leaves, on IFN-γ/TNF-α-induced expression of MDC/CCL22 and on skin inflammation in animal models. Our results showed that spinasterol-Glc inhibited mRNA and protein expression of MDC/CCL22 in TNF-α/IFN-γ-stimulated HaCaT keratinocytes in dose-dependent manners. We found that spinasterol-Glc inhibited IFN-γ/TNF-α -induced activation of NF-κB and STAT1. Inhibitors for NF-κB(Bay11-7085), JAK/STAT (AG490), p38 (SB203580) reduced production of MDC/CCL22 in HaCaT cells, indicating that spinalsterol-Glc inhibits expression of MDC/CCL22 via p38 and JAK signaling pathways and the downstream NF-κB and STAT fa...