Abstract
Chronic inflammatory skin diseases, such as atopic dermatitis, are caused by the accumulation of immune cells and the overproduction of chemokines, including CCL17 and CCL22, due to the activation of pro-inflammatory cytokines secreted from keratinocytes. In the present study, the inhibitory activity of HM-V on tumor necrosis factor alpha (TNF-α)/interferon gamma (IFN-γ)-induced pro-inflammatory cytokines was examined in human keratinocytes (HaCaTs) and 2,4-dinitrofluorobenzene (DNCB)-induced chronic skin contact dermatitis animal models. Traditional Asian medicinal herb extracts mixture (HM-V), which have been extensively used in Asian medicine, were utilized. In TNF-α/IFN-γ-induced HaCaTs, HM-V strongly inhibited mRNA and protein expression of CCL17 and CCL22 in a concentration-dependent manner. The expression of pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 was also inhibited. Therefore, localized administration of HM-V in the DNCB-induced animal model alleviated immune cell deposition and skin inflammation. The results indicate that HM-V exerts inhibitory effects on keratinocyte production of CCL17 and CCL22. Furthermore, HM-V may be a useful anti-inflammatory agent for the prevention and treatment of inflammatory skin diseases.