Apamin inhibits TNF-α- and IFN-γ-induced inflammatory cytokines and chemokines via suppressions of NF-κB signaling pathway and STAT in human keratinocytes

Background atopic dermatitis (ad) is identified by an increase in infiltrations of several inflammatory cells including type 2 helper (th2) lymphocytes. th2-related chemokines such as thymus and activation-regulated chemokine (tarc/ccl17) and macrophage-derived chemokine (mdc/ccl22),and pro-inflammatory cytokines including interleukin (il)-1β and il-6 are considered to play a crucial role in ad. tumor necrosis factor (tnf)-α- and interferon (ifn)-γ induce the inflammatory condition through production of tarc,mdc,il-1β and il-6,and activations of related transcription factors,such as nuclear factor kappa-light-chain-enhancer of activated b cells (nf-κb) and signal transducer and activator of transcription (stat) in keratinocytes. apamin,a peptide component of bee venom,has been reported its beneficial activities in various diseases. however,anti-inflammatory effects of apamin on inflammatory condition in keratinocytes have not been explored. therefore,the present study aimed to demonstrate the anti-inflammatory effect of apamin on tnf-α- and ifn-γ-induced inflammatory condition in keratinocytes. methods hacat was used as human keratinocytes cell line. cell counting kit-8 was performed to measure a cytotoxicity of apamin. the effects of apamin on tnf-α-/ifn-γ-induced inflammatory condition were determined by real-time pcr and western blot analysis. further,nf-κb signaling pathways,stat1,and stat3 were analyzed by western blot and immunofluorescence. results apamin ameliorated the inflammatory condition through suppression of th2-related chemokines and pro-inflammatory cytokines. further,apamin down-regulated the activations of nf-κb signaling pathways and stats in hacat cells. conclusions these results suggest that apamin has therapeutic effect on ad through improvement of inflammatory condition. © 2017 institute of pharmacology,polish academy of sciences