Caffeic acid phenethyl ester promotes anti-inflammatory effects by inhibiting MAPK and NF-κB signaling in activated HMC-1 human mast cells

Abstract

Context: Caffeic acid phenethyl ester (CAPE), an active component of honeybee propolis, is known to have antioxidant, anti-inflammatory, and other beneficial medicinal properties. However, the molecular mechanisms underlying its anti-allergic effects in mast cells are unknown. Objective: The purpose of the present study was to examine whether CAPE modulates the immunoglobulin E (IgE)-mediated local allergic reaction in animals, as well as to elucidate the effects of CAPE on mast cells in vitro. Materials and methods: To investigate the bioactive potential of CAPE (10 or 20μM), HMC-1 cells were stimulated with phorbol 12-myristate 13-acetate plus calcium ionophore A23187 (PMACI) for 24h in the presence or absence of CAPE. To study the pharmacological effects of CAPE, enzyme-linked immunosorbent assays (ELISAs), RT-PCR, Western blot analysis, electrophoretic mobility shift assays (EMSAs), and fluorescence assays were used. Results: CAPE (10mg/kg) inhibited local IgE-mediated allergic reactions (0.164 versus 0.065 O.D.) in a mouse model. Additionally, CAPE (20μM) attenuated PMACI-stimulated histamine release (3146.42 versus 2564.83pg/ml) and the production of inflammatory cytokines, such as interleukin (IL)-1β (4.775 versus 0.713pg/ml, IC50=6.67μM), IL-6 (4771.5 versus 449.1pg/ml, IC50=5.25μM), and IL-8 (5991.7 versus 2213.1pg/ml, IC50=9.95μM) in HMC-1 cells. In activated HMC-1 cells, pretreatment with CAPE decreased the phosphorylation of c-Jun N-terminal kinase. In addition, CAPE inhibited PMACI-induced nuclear factor (NF)-κB activation by suppressing IκBα phosphorylation and its degradation. Discussion and conclusion: Our results indicated that CAPE can modulate mast cell-mediated allergic disease. © 2014 Informa Healthcare USA, Inc.