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 factors activated by IFN‐γ/TNF‐α. Furthermore, we demonstrated that topical administration of spinasterol‐Glc reduced epidermal thickness and infiltration of inflammatory cells compare to positive control. Levels of serum histamine and IgE were also decreased after the application of spinasterol‐Glc. Our results suggest that spinasterol‐Glc may have significant effects on improving AD‐like conditions via inhibiting expression of inflammatory cytokines and chemokines including MDC/CCL22.