title: Non-thermal plasma activates human keratinocytes by stimulation of antioxidant and phase II pathways.
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.
authors.affiliation: From the Centre for Innovation Competence (ZIK) plasmatis and Leibniz Institute for Plasma Science and Technology, Felix-Hausdorff-Strasse 2, 17489 Greifswald, Germany anke.schmidt@inp-greifswald.de.
authors.forename: Anke
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: From the Centre for Innovation Competence (ZIK) plasmatis and.
authors.forename: Stephan
authors.initials: S
authors.lastname: Dietrich
authors.affiliation: Leibniz Institute for Plasma Science and Technology, Felix-Hausdorff-Strasse 2, 17489 Greifswald, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Steuer
authors.affiliation: Leibniz Institute for Plasma Science and Technology, Felix-Hausdorff-Strasse 2, 17489 Greifswald, Germany.
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Weltmann
authors.affiliation: Leibniz Institute for Plasma Science and Technology, Felix-Hausdorff-Strasse 2, 17489 Greifswald, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: von Woedtke
authors.affiliation: From the Centre for Innovation Competence (ZIK) plasmatis and.
authors.forename: Kai
authors.initials: K
authors.lastname: Masur
authors.affiliation: From the Centre for Innovation Competence (ZIK) plasmatis and.
authors.forename: Kristian
authors.initials: K
authors.lastname: Wende
mesh_terms: D000975:Antioxidants / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D058626:Plasma Gases / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D059467:Transcriptome / Q000187:drug effects
chemical_list: D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D058626:Plasma Gases; D034741:RNA, Small Interfering; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; D005978:Glutathione
keywords: Gene Expression; Keratinocyte; Oxidative Stress; Reactive Nitrogen Species (RNS); Reactive Oxygen Species (ROS)