Inhibitory effect action mechanism of dieckol on the production of MDC/CCL22 in interferon-γ stimulated HaCaT human keratinocytes

Abstract

Macrophage-derived chemokine, C-C motif chemokine 22 (MDC/CCL22), is one of the inflammatory chemokines that controls the movement of monocytes, monocyte-derived dendritic cells, and natural killer cells. MDC/CCL22 is a ligand for CC chemokine receptor 4, which is expressed in T-helper type 2 cells. MDC/CCL22 in serum and skin lesions is elevated in atopic dermatitis, which suggests that chemokines produced from keratinocytes are responsible for attracting inflammatory lymphocytes to the skin. Keratinocyte is a cell type in the epidermis, the outer layer of the skin. Keratinocytes grow continuously by mitosis until they reach the upper epidermal layers. A major signaling pathway in the interferon-γ (IFN-γ)-stimulated inflammation response involves the signal transducers and activators of transcription 1 (STAT1). IFN-γ signals regulate phosphorylation of STAT1 and production of MDC/CCL22. We investigated the inhibitory effect and mechanism of action of dieckol in IFN-γ-stimulated HaCaT human keratinocytes. Dieckol inhibited MDC/CCL22 production, which was induced by 10 ng/mL of IFN-γ. Effective concentrations (5 and 10 μM) of dieckol suppressed the phosphorylation of STAT1 in a dose-dependent manner. STAT1 is an important key transcription factor in the IFN-γ signaling pathway. Dieckol also slightly suppressed the phosphorylation of the extracellular signal-regulated kinases (ERK) pathway. ERK is one of the MAP kinases. Results suggest that dieckol affects the inflammation inhibition effect by regulating STAT1 phosphorylation and can prevent inflammation.