(2S)-2′-Methoxykurarinone from Sophora flavescens Suppresses Cutaneous T Cell-Attracting Chemokine/CCL27 Expression Induced by Interleukin-β/Tumor Necrosis Factor-α via Heme Oxygenase-1 in Human Keratinocytes

다국어 초록 (Multilingual Abstract)

One of the CC chemokines, cutaneous T cell-attracting chemokine (CTACK/CCL27), is a skin-specific CC chemokine that is produced constitutively by keratinocytes and is highly up-regulated in inflammatory skin conditions such as atopic dermatitis and contact dermatitis. (2S)-2′-Methoxykurarinone (MOK) from Sophora flavescens has been demonstrated to have antioxidant effects. Heme oxygenase (HO)-1 has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types. This study aimed to define whether and how MOK regulates skin specific CTACK/CCL27 chemokine production in human HaCaT keratinocytes. The level of CTACK/CCL27 and HO-1 expression was measured by reverse transcription-polymerase chain reaction, and signaling was evaluated by western blot analysis. CTACK/CCL27 production was determined by enzyme-linked immunosorbent assay. Pretreatment with MOK suppressed tumor necrosis factor-α (TNF-α)- and interleukin (IL)-1β-induced CTACK/CCL27 production in human HaCaT keratinocytes. MOK inhibited TNF-α- and IL-1β-induced nuclear factor κB (NF-κB) activation. Interestingly, pretreatment with MOK significantly suppressed TNF-α- and IL-1β-induced CTACK/CCL27 production through the induction of HO-1. This suppression was completely abolished by HO-1 small interfering RNA. Furthermore, carbon monoxide, but not other end products of HO-1 activity, also suppressed TNF-α- and IL-1β-induced CTACK/CCL27 production. These results demonstrate that MOK attenuates TNF-α- and IL-1β-induced production of CTACK/CCL27 in human HaCaT keratinocytes by inhibiting NF-κB activation and induction of HO-1.

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