7,8-dimethoxycoumarin Attenuates the Expression of IL-6, IL-8, and CCL2/MCP-1 in TNF-α-Treated HaCaT Cells by Potentially Targeting the NF-κB and MAPK Pathways

7,8-dimethoxycoumarin (DMC, C11H10O4), a natural coumarin compound, is present in <i>Citrus</i> plants including <i>Citrus decumana</i> and grapefruit. It is known to have protective effects on the kidneys against Cisplatin and ischemia-reperfusion injury. However, the underlying mechanisms of its inhibitory effects on skin inflammation have not been investigated in vitro. Tumor necrosis factor (TNF)-&#945; is known to be one of the main causative agents of skin inflammation. It induces pro-inflammatory cytokines and chemokines by activating nuclear factor-&#954;B (NF-&#954;B) and mitogen-activated protein kinase (MAPK) signaling. In this study, we investigated the inhibitory effect of DMC on the expression of pro-inflammatory cytokines and chemokines in TNF-&#945;-treated human keratinocyte HaCaT cells. Pretreatment with DMC inhibited TNF-&#945;-treated cytokines (interleukin 6; IL-6) and chemokines (IL-8 and monocyte chemoattractant protein-1). In addition, DMC significantly inhibited TNF-&#945;-treated NF-&#954;B activation and phosphorylation of MAPKs, such as c-Jun N-terminal kinases (JNK) and extracellular-signal-regulated kinase (ERK). These results suggest that DMC may elicit an anti-inflammatory response by suppressing TNF-&#945;-treated activation of NF-&#954;B and MAPK pathways in keratinocytes. Hence, it might be a useful therapeutic drug against skin inflammatory diseases.

Abstract licence: CC BY

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