Suppression of skin inflammation in keratinocytes and acute/chronic disease models by caffeic acid phenethyl ester
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Skin inflammation plays a central role in the pathophysiology and symptoms of diverse chronic skin diseases including atopic dermatitis (AD). In this study, we examined if caffeic acid phenethyl ester (CAPE), a skin-permeable bioactive compound from propolis, was protective against skin inflammation using in vitro cell system and in vivo animal disease models. CAPE suppressed TNF-α-induced NF-κB activation and expression of inflammatory cytokines in human keratinocytes (HaCaT). The potency and efficacy of CAPE were superior to those of a non-phenethyl derivative, caffeic acid. Consistently, topical treatment of CAPE (0.5 %) attenuated 12-O-tetradecanoylphorbol-13-acetate(TPA)-induced skin inflammation on mouse ear as CAPE reduced ear swelling and histologic inflammation scores. CAPE suppressed increased expression of pro-inflammatory molecules such as TNF-α, cyclooxygenase-2 and inducible NO synthase in TPA-stimulated skin. TPA-induced phosphorylation of IκB and ERK was blocked by CAPE suggesting that protective effects of CAPE on skin inflammation is attributed to inhibition of NF-κB activation. Most importantly, in an oxazolone-induced chronic dermatitis model, topical application of CAPE (0.5 and 1 %) was effective in alleviating AD-like symptoms such as increases of trans-epidermal water loss, skin thickening and serum IgE as well as histologic inflammation assessment. Collectively, our results propose CAPE as a promising candidate for a novel topical drug for skin inflammatory diseases.
KeywordsCaffeic acid phenethyl ester (CAPE) Skin inflammation Nuclear factor κB (NF-κB) Atopic dermatitis TPA-induced ear edema
KM-Lim designed and JE-Koo, ES-Kim, ON-Bae performed experiments. SJ-Bae analyzed the data. KM-Lim and JY-Lee wrote the manuscript. Authors thank Chae-Wook Lee for technical support for experiments. This study was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korean government (MEST) (NRF-2012R1A1A3004541), and the Research Fund, 2013 of the Catholic University of Korea.
Conflict of interest
The authors declare no conflict of interest.
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