3,4,5-Tricaffeoylquinic acid inhibits tumor necrosis factor-I+/--stimulated production of inflammatory mediators in keratinocytes via suppression of Akt- and NF-I super(o)B-pathways

Keratinocytes may play an important role in the pathogenesis of skin disease in atopic dermatitis. Caffeoyl derivatives are demonstrated to have anti-inflammatory and anti-oxidant effects. However, the effect of 3,4,5-tricaffeoylquinic acid prepared from Aconium koreanum on the pro-inflammatory cytokine-stimulated keratinocyte responses remains uncertain. In human keratinocytes, we investigated the effect of 3,4,5-tricaffeoylquinic acid on the tumor necrosis factor (TNF)-I+/--stimulated production of inflammatory mediators in relation to the nuclear factor (NF)-I super(o)B and cell signaling Akt, which regulates the transcription genes involved in immune and inflammatory responses. 3,4,5-Tricaffeoylquinic acid inhibited the TNF-I+/--stimulated production of cytokines (IL-1I super(2) and IL-8) and chemokine (CCL17 and CCL27) in keratinocytes. Bay 11-7085 (an inhibitor of NF-I super(o)B activation) and Akt inhibitor attenuated the TNF-I+/--induced formation of inflammatory mediators. 3,4,5-Tricaffeoylquinic acid, Bay 11-7085, Akt inhibitor and N-acetylcysteine inhibited the TNF-I+/--induced activation of NF-I super(o)B, activation of Akt, and formation of reactive oxygen and nitrogen species. The results show that 3,4,5-tricaffeoylquinic acid seems to attenuate the TNF-I+/--stimulated inflammatory mediator production in keratinocytes by suppressing the activation of Akt and NF-I super(o)B pathways which may be mediated by reactive oxygen species. The findings suggest that 3,4,5-tricaffeoylquinic acid may exert an inhibitory effect against the pro-inflammatory mediator-induced skin disease.