title: Impact of non-thermal plasma treatment on MAPK signaling pathways of human immune cell lines.
abstract: In the field of wound healing research non-thermal plasma (NTP) increasingly draws attention. Next to its intensely studied antibacterial effects, some studies already showed stimulating effects on eukaryotic cells. This promises a unique potential in healing of chronic wounds, where effective therapies are urgently needed. Immune cells do play an important part in the process of wound healing and their reaction to NTP treatment has yet been rarely examined. Here, we studied the impact of NTP treatment using the kinpen on apoptotic and proliferative cell signaling pathways of two human immune cell lines, the CD4(+)T helper cell line Jurkat and the monocyte cell line THP-1. Depending on NTP treatment time the number of apoptotic cells increased in both investigated cell types according to a caspase 3 assay. Western blot analysis pointed out that plasma treatment activated pro-apoptotic signaling proteins like p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase 1 and 2 (JNK 1/2) in both cell types. Stronger signals were detected in Jurkat cells at comparable plasma treatment times. Intriguingly, exposure of Jurkat and THP-1 cells to plasma also activated the pro-proliferative signaling molecules extracellular signal-regulated kinase 1/2 (ERK 1/2) and MAPK/ERK kinase 1 and 2 (MEK 1/2). In contrast to Jurkat cells, the anti-apoptotic heat shock protein 27 (HSP27) was activated in THP-1 cells after plasma treatment, indicating a possible mechanism how THP-1 cells may reduce programmed cell death. In conclusion, several signaling cascades were activated in the examined immune cell lines after NTP treatment and in THP-1 monocytes a possible defense mechanism against plasma impacts could be revealed. Therefore, plasma might be a treatment option for wound healing.
authors.affiliation: Center for Innovation Competence, Felix-Hausdorff-Str. 2, 17489 Greifswald, Germany. lena.bundscherer@inp-greifswald.de
authors.forename: Lena
authors.initials: L
authors.lastname: Bundscherer
authors.forename: Kristian
authors.initials: K
authors.lastname: Wende
authors.forename: Katja
authors.initials: K
authors.lastname: Ottmüller
authors.forename: Annemarie
authors.initials: A
authors.lastname: Barton
authors.forename: Anke
authors.initials: A
authors.lastname: Schmidt
authors.forename: Sander
authors.initials: S
authors.lastname: Bekeschus
authors.forename: Sybille
authors.initials: S
authors.lastname: Hasse
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Weltmann
authors.forename: Kai
authors.initials: K
authors.lastname: Masur
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lindequist
mesh_terms: D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D053148:Caspase 3 / Q000378:metabolism; D049109:Cell Proliferation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D020935:MAP Kinase Signaling System / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D009928:Organ Specificity; D058626:Plasma Gases / Q000378:metabolism*; D014945:Wound Healing / Q000276:immunology
chemical_list: D055551:HSP27 Heat-Shock Proteins; D058626:Plasma Gases; D048049:Extracellular Signal-Regulated MAP Kinases; D053148:Caspase 3
keywords: Caspase 3; ERK; HSP27; JNK; Jurkat cells; MAPK signaling; MAPK/ERK kinase; MAPKs; MEK; NTP; Non-thermal plasma; Plasma medicine; RNS; ROS; SLm; THP-1 cells; Wound healing; c-Jun N-terminal kinase; extracellular signal-regulated kinase; heat shock protein 27; mitogen-activated protein kinases; non-thermal plasma; p38 MAPK; p38 mitogen-activated protein kinase; reactive nitrogen species; reactive oxygen species; standard liters per minute