Surface air plasma-induced cell death and cytokine release of human keratinocytes in the context of psoriasis.
BACKGROUND
Cold atmospheric plasma (CAP) has shown promise for wound healing, although little is understood of the underpinning mechanisms. Little has been reported so far of its potential use in the treatment of immune-mediated diseases such as psoriasis.


OBJECTIVE
To study CAP-induced cell death and cytokine release in human keratinocytes as a first assessment of possible CAP use for psoriasis.


METHODS
Using a CAP generator free of energetic ions, we observed its effects on keratinocytes in terms of morphology, cell viability and apoptosis, intracellular and mitochondrial reactive oxygen species (ROS), lysosomal integrity and mitochondrial membrane potential; and on secretion and expression of eight cytokines at protein and gene levels.


RESULTS
CAP-induced reduced cell viability, apoptotic death and production of intracellular and mitochondrial ROS in dose-dependent manner. Mitochondrial dysfunction and lysosomal leakage were found in CAP-treated cells. It also induced release of interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF), and enhanced the mRNA expression of IL-1β, IL-6, IL-8, IL-10, TNF-α, interferon-γ and VEGF. By contrast, IL-12 declined monotonically.


CONCLUSIONS
The results suggest that with appropriate control of its dose, physical plasma could induce cell death via apoptotic pathways and enable simultaneous reduction in IL-12. These effects may be used to suppress keratinocyte hyperproliferation and to target T-cell activation to control amplification of inflammation. This provides an initial basis for further studies of CAP as a potential therapeutic option for inflammatory and immune-related diseases in dermatology, including psoriasis.
Department of Dermatology, Xi'an Jiaotong University, Xi'an 710049, China.|Center of Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an, 710049, China.
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Zhong
Department of Dermatology, Xi'an Jiaotong University, Xi'an 710049, China.|Center of Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an, 710049, China.
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Dong
Center of Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an, 710049, China.|School of Electrical Engineering, Xi'an Jiaotong University, Xi'an, 710049, China.
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Liu
Center of Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an, 710049, China.
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Xu
Department of Dermatology, Xi'an Jiaotong University, Xi'an 710049, China.
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Xiao
Center for Bioelectrics, Old Dominion University, Norfolk, VA, 23508, U.S.A.
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Chen
Center of Plasma Biomedicine, State Key Laboratory of Electrical Insulation and Power Equipment, Xi'an Jiaotong University, Xi'an, 710049, China.|School of Electrical Engineering, Xi'an Jiaotong University, Xi'an, 710049, China.|Center for Bioelectrics, Old Dominion University, Norfolk, VA, 23508, U.S.A.
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Kong
D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015603:Keratinocytes / Q000378:metabolism* / Q000473:pathology; D008247:Lysosomes / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000737:chemistry; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D010949:Plasma; D011565:Psoriasis / Q000628:therapy*; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D016207:Cytokines; D009566:Nitrates; D009573:Nitrites; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D053148:Caspase 3; D053453:Caspase 9