Abstract
Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. By spatial and time-resolved delivery of reactive oxygen and nitrogen species, it allows stimulation or inhibition of cellular processes in biological systems. Our data show that both gene and protein expression is highly affected by non-thermal plasma. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. Additionally, glutathione metabolism, which is a marker for NRF2-related signaling events, was affected. Among the most robustly increased genes and proteins, heme oxygenase 1, NADPH-quinone oxidoreductase 1, and growth factors were found. The roles of NRF2 targets, investigated by siRNA silencing, revealed that NRF2 acts as an important switch for sensing oxidative stress events. Moreover, the influence of non-thermal plasma on the NRF2 pathway prepares cells against exogenic noxae and increases their resilience against oxidative species. Via paracrine mechanisms, distant cells benefit from cell-cell communication. The finding that non-thermal plasma triggers hormesis-like processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application.
Highlights
Non-thermal plasma provides an interesting therapeutic opportunity to control redox-based processes, e.g. wound healing
We investigated its effects on mRNA and protein levels to identify possible applications of non-thermal plasma in keratinocytes, e.g. in acceleration of wound healing and re-epithelialization
H2O2 is an important second messenger for growth factors released during the wound healing process and has been shown to increase keratinocyte viability and migration in a wound model [45]
Summary
Non-thermal plasma provides an interesting therapeutic opportunity to control redox-based processes, e.g. wound healing. Non-thermal atmospheric pressure plasma provides a novel therapeutic opportunity to control redox-based processes, e.g. wound healing, cancer, and inflammatory diseases. Nuclear factor erythroid-related factor 2 (NRF2) and phase II enzyme pathway components were found to act as key controllers orchestrating the cellular response in keratinocytes. The finding that non-thermal plasma triggers hormesislike processes in keratinocytes facilitates the understanding of plasma-tissue interaction and its clinical application. Non-thermal plasma was described to have antimicrobial activity and to play an important role in the killing of microorganisms [2,3,4,5] These developments resulted in a new and independent field, plasma medicine, in which one promising approach is to promote wound closure by stimulation of the cells involved.
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