Non-thermal atmospheric pressure plasma-induced IL-8 expression is regulated via intracellular K+ loss and subsequent ERK activation in human keratinocyte HaCaT cells

Non-thermal atmospheric pressure plasma (NTAPP) has recently emerged as a novel medical therapy for skin wounds. Interleukin-8 (IL-8) is thought to play a critical role in wound healing. NTAPP irradiation has been reported to promote production of IL-8; however, the mechanism is not fully understood. The aim of this study was to elucidate the underlying mechanism of NTAPP-induced IL-8 expression in human keratinocyte HaCaT cells. NTAPP irradiation of HaCaT cells increased IL-8 mRNA expression in an irradiation time-dependent manner. Although hydrogen peroxide (H2O2) was generated in culture medium irradiated with NTAPP, treatment of HaCaT cells with H2O2 itself failed to induce the expression. In addition, we found that NTAPP irradiation of HaCaT cells decreased intracellular K+ levels. High intracellular K+ concentrations suppressed NTAPP-induced IL-8 mRNA expression, and the K+ ionophore valinomycin (Val) enhanced the induction of IL-8 mRNA. Moreover, NTAPP stimulated activation of ERK MAP kinase and the ERK inhibitor prevented NTAPP-induced IL-8 mRNA expression. NTAPP-induced ERK activation was inhibited in the presence of high concentrations of extracellular K+ and enhanced in the presence of Val. Taken together, these findings suggest that NTAPP irradiation stimulates intracellular K+ loss and subsequent ERK activation, leading to the induction of IL-8 expression.