Allergic skin inflammation such as atopic dermatitis (AD) is characterized by edema and infiltration with various inflammatory cells such as mast cells, T cells and macrophages. Macrophages are important player that involved inflammation process including initiation, propagation, and resolution. Interleukin-6 (IL-6) is a representative pro-inflammatory cytokine generated in stimulated macrophage and induces deleterious inflammatory states. This study was conducted to investigate the anti-inflammatory effect and action mechanism of DPHC in the RAW 264.7 murine macrophages and AD mice model. DPHC inhibit LPS-induced IL-6 production in a dose dependent manner and suppressed the phosphorylation or the nuclear translocation of NF-κB, a central signaling molecule in LPS induced inflammation process. Furthermore, the known inhibitors of NF-κB (pyrrolidine dithiocarbamate; PDTC, N-tosyl-Lphenylalanine chloromethyl ketone; TPCK, Parthenolide) strongly inhibited IL-6 production. However, DPHC had no or only minimal effects on the mitogen activated protein kinase pathways (JNK, ERK and P-38) and STAT1, 3, and 5 pathways activated by LPS. In AD mice model, the DPHC-treated group showed significantly decreased immunoglobulin E (IgE), ear thickness and inflammatory cell infiltration compared with the induction group. In addition, DPHC treatment resulted in a smaller lymph node size with reduced the thickness and length compared to the induction group. These results suggest that DPHC may be effective in treating the allergic symptoms of AD. This work was supported by the National Research Foundation of Korea Grant funded by the Korean Government (MEST) (NRF-C1ABA001-2011-0021039).

Keywords: Diphlorethohydroxycarmalol, Atopic dermatitis, IL-6, immunoglobulin E