title: Periodic Exposure of Keratinocytes to Cold Physical Plasma: An In Vitro Model for Redox-Related Diseases of the Skin.
abstract: Oxidative stress illustrates an imbalance between radical formation and removal. Frequent redox stress is critically involved in many human pathologies including cancer, psoriasis, and chronic wounds. However, reactive species pursue a dual role being involved in signaling on the one hand and oxidative damage on the other. Using a HaCaT keratinocyte cell culture model, we investigated redox regulation and inflammation to periodic, low-dose oxidative stress after two, six, eight, ten, and twelve weeks. Chronic redox stress was generated by recurrent incubation with cold physical plasma-treated cell culture medium. Using transcriptome microarray technology, we identified both acute ROS-stress responses as well as numerous adaptions after several weeks of redox challenge. We determined a differential expression (2-fold, FDR < 0.01, p < 0.05) of 260 genes that function in inflammation and redox homeostasis, such as cytokines (e.g., IL-6, IL-8, and IL-10), growth factors (e.g., CSF2, FGF, and IGF-2), and antioxidant enzymes (e.g., HMOX, NQO1, GPX, and PRDX). Apoptotic signaling was affected rather modestly, especially in p53 downstream targets (e.g., BCL2, BBC3, and GADD45). Strikingly, the cell-protective heat shock protein HSP27 was strongly upregulated (p < 0.001). These results suggested cellular adaptions to frequent redox stress and may help to better understand the inflammatory responses in redox-related diseases.
authors.affiliation: Leibniz-Institute for Plasma Science and Technology (INP Greifswald), ZIK plasmatis, Felix-Hausdorff-Strasse 2, 17489 Greifswald, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Schmidt
authors.affiliation: Leibniz-Institute for Plasma Science and Technology (INP Greifswald), ZIK plasmatis, Felix-Hausdorff-Strasse 2, 17489 Greifswald, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: von Woedtke
authors.affiliation: Leibniz-Institute for Plasma Science and Technology (INP Greifswald), ZIK plasmatis, Felix-Hausdorff-Strasse 2, 17489 Greifswald, Germany.
authors.forename: Sander
authors.initials: S
authors.lastname: Bekeschus
mesh_terms: D000975:Antioxidants / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000096:biosynthesis; D058626:Plasma Gases / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012871:Skin Diseases / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
chemical_list: D000975:Antioxidants; D016207:Cytokines; D058626:Plasma Gases; D017382:Reactive Oxygen Species; D010088:Oxidoreductases