BACKGROUND AND PURPOSE: Microbial product lipopolysaccharide (LPS) has been shown to be involved in the pathogenesis of inflammatory skin diseases. Caffeoyl derivatives have demonstrated anti-inflammatory and antioxidant effects. However, the effect of 3,4,5-tricaffeoylquinic acid (3,4,5-triCQA) on the production of microbial product-induced inflammatory mediators in keratinocytes has not yet been studied. EXPERIMENTAL APPROACH: Using human keratinocytes, we investigated the effect of 3,4,5-triCQA on the LPS-stimulated production of inflammatory mediators in relation to the nuclear factor (NF)-ĸB, Akt and ERK pathways. RESULTS: 3,4,5-triCQA inhibited the LPS-induced expression of Toll-like receptor 4, and the production of cytokines and chemokines in keratinocytes. 3,4,5-triCQA, Bay 11-7085, Aĸt inhibitor and ERK inhibitor each attenuated the LPS-induced production of inflammatory mediators by inhibiting the NF-ĸB, Akt and ERK pathways. CONCLUSIONS AND IMPLICATIONS: 3,4,5-triCQA may attenuate the LPS-stimulated production of inflammatory mediators in keratinocytes by suppressing the Toll-like receptor 4 expression-mediated activation of the Akt, ERK and NF-ĸB pathways. 3,4,5-triCQA may exert a preventive effect against microbial product-induced inflammatory skin diseases.
BACKGROUND AND PURPOSE: Microbial product lipopolysaccharide (LPS) has been shown to be involved in the pathogenesis of inflammatory skin diseases. Caffeoyl derivatives have demonstrated anti-inflammatory and antioxidant effects. However, the effect of 3,4,5-tricaffeoylquinic acid (3,4,5-triCQA) on the production of microbial product-induced inflammatory mediators in keratinocytes has not yet been studied. EXPERIMENTAL APPROACH: Using human keratinocytes, we investigated the effect of 3,4,5-triCQA on the LPS-stimulated production of inflammatory mediators in relation to the nuclear factor (NF)-ĸB, Akt and ERK pathways. RESULTS:3,4,5-triCQA inhibited the LPS-induced expression of Toll-like receptor 4, and the production of cytokines and chemokines in keratinocytes. 3,4,5-triCQA, Bay 11-7085, Aĸt inhibitor and ERK inhibitor each attenuated the LPS-induced production of inflammatory mediators by inhibiting the NF-ĸB, Akt and ERK pathways. CONCLUSIONS AND IMPLICATIONS: 3,4,5-triCQA may attenuate the LPS-stimulated production of inflammatory mediators in keratinocytes by suppressing the Toll-like receptor 4 expression-mediated activation of the Akt, ERK and NF-ĸB pathways. 3,4,5-triCQA may exert a preventive effect against microbial product-induced inflammatory skin diseases.