Improved Wound Healing of Airway Epithelial Cells Is Mediated by Cold Atmospheric Plasma: A Time Course-Related Proteome Analysis

The promising potential of cold atmospheric plasma (CAP) treatment as a new therapeutic option in the field of medicine, particularly in Otorhinolaryngology and Respiratory medicine, demands primarily the assessment of potential risks and the prevention of any direct and future cell damages. Consequently, the application of a special intensity of CAP that is well tolerated by cells and tissues is of particular interest. Although improvement of wound healing by CAP treatment has been described, the underlying mechanisms and the molecular influences on human tissues are so far only partially characterized. In this study, human S9 bronchial epithelial cells were treated with cold plasma of atmospheric pressure plasma jet that was previously proven to accelerate the wound healing in a clinically relevant extent. We studied the detailed cellular adaptation reactions for a specified plasma intensity by time-resolved comparative proteome analyses of plasma treated vs. nontreated cells to elucidate the mechanisms of the observed improved wound healing and to define potential biomarkers and networks for the evaluation of plasma effects on human epithelial cells. K-means cluster analysis and time-related analysis of fold-change factors indicated concordantly clear differences between the short-term (up to 1 h) and long-term (24-72 h) adaptation reactions. Thus, the induction of Nrf2-mediated oxidative and endoplasmic reticulum stress response, PPAR-alpha/RXR activation as well as production of peroxisomes, and prevention of apoptosis already during the first hour after CAP treatment are important cell strategies to overcome oxidative stress and to protect and maintain cell integrity and especially microtubule dynamics. After resolving of stress, when stress adaptation was accomplished, the cells seem to start again with proliferation and cellular assembly and organization. The observed strategies and identification of marker proteins might explain the accelerated wound healing induced by CAP, and these indicators might be subsequently used for risk assessment and quality management of application of nonthermal plasma sources in clinical settings.

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The wound healing capacity of undifferentiated and differentiated airway epithelial cells in vitro

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2018.07.006 ◽

2018 ◽

Vol 112 ◽

pp. 163-168 ◽

Cited By ~ 2

Author(s):

Cynthia M. Schwartz ◽

Braedyn A. Dorn ◽

Selam Habtemariam ◽

Cynthia L. Hill ◽

Tendy Chiang ◽

...

Keyword(s):

Wound Healing ◽

Epithelial Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial

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Tissue Factor Facilitates Wound Healing in Human Airway Epithelial Cells

CHEST Journal ◽

10.1016/j.chest.2018.10.007 ◽

2019 ◽

Vol 155 (3) ◽

pp. 534-539 ◽

Cited By ~ 3

Author(s):

Michael D. Davis ◽

Isao Suzaki ◽

Shuichi Kawano ◽

Kosaku Komiya ◽

Qing Cai ◽

...

Keyword(s):

Wound Healing ◽

Epithelial Cells ◽

Tissue Factor ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Human Airway ◽

Human Airway Epithelial Cells

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Promotion of Wound Healing of Genetic Diabetic Mice Treated by a Cold Atmospheric Plasma Jet

IEEE Transactions on Plasma Science ◽

10.1109/tps.2019.2928320 ◽

2019 ◽

Vol 47 (11) ◽

pp. 4848-4860 ◽

Cited By ~ 3

Author(s):

Donghai Li ◽

Guiling Li ◽

Jing Li ◽

Zhi-Qiang Liu ◽

Xuman Zhang ◽

...

Keyword(s):

Wound Healing ◽

Plasma Jet ◽

Atmospheric Plasma ◽

Diabetic Mice ◽

Cold Atmospheric Plasma

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Comparative Study between Direct and Indirect Treatment with Cold Atmospheric Plasma on In Vitro and In Vivo Models of Wound Healing

Plasma Medicine ◽

10.1615/plasmamed.2019028659 ◽

2018 ◽

Vol 8 (4) ◽

pp. 379-401 ◽

Cited By ~ 1

Author(s):

Constance Duchesne ◽

Nadira Frescaline ◽

Jean-Jacques Lataillade ◽

Antoine Rousseau

Keyword(s):

Wound Healing ◽

Comparative Study ◽

Atmospheric Plasma ◽

In Vivo Models ◽

Cold Atmospheric Plasma ◽

Indirect Treatment

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Airway epithelial tight junctions and binding and cytotoxicity ofPseudomonas aeruginosa

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1999.277.1.l204 ◽

1999 ◽

Vol 277 (1) ◽

pp. L204-L217 ◽

Cited By ~ 24

Author(s):

Alfred Lee ◽

Dar Chow ◽

Brian Haus ◽

Wanru Tseng ◽

David Evans ◽

...

Keyword(s):

Epithelial Cells ◽

Tight Junctions ◽

Propidium Iodide ◽

Time Course ◽

Living Cells ◽

Airway Epithelial Cells ◽

Airway Epithelial ◽

Basolateral Membranes ◽

Free Edges

The role of tight junctions in the binding and cytoxicity of Pseudomonas aeruginosato apical or basolateral membranes of lung airway epithelial cells was tested with fluorescence microscopy on living cells. Binding of noncytotoxic P. aeruginosa strain O1 was assessed with P. aeruginosa that expressed green fluorescent protein. Binding of cytotoxic P. aeruginosa strain 6206 was assessed with FITC-labeled P. aeruginosa; cytotoxicity was determined from nuclear uptake of the impermeant dye propidium iodide. The role of direct contact of P. aeruginosa to epithelial cells was tested with filters with small (0.45-μm) or large (2.0-μm) pores. High transepithelial resistance ( Rt) Calu-3 and cultured bovine tracheal monolayers ( Rt> 1,000 Ω ⋅ cm2) bound P. aeruginosa very infrequently (<1 P. aeruginosa/100 cells) at the apical membrane, but P. aeruginosabound frequently to cells near “free edges” at holes, wounds, islands, and perimeters; cytotoxicity required direct interaction with basolateral membranes. Wounded high Rtepithelia showed increased P. aeruginosa binding and cytotoxicity at the free edges because basolateral membranes were accessible to P. aeruginosa, and dead and living cells near the wound bound P. aeruginosa similarly. Compared with high Rtepithelia, low RtCFT1 ( Rt= 100–200 Ω ⋅ cm2) and EGTA-treated Calu-3 monolayers were 25 times more susceptible to P. aeruginosa binding throughout the monolayer. Cytotoxicity to CFT1 cells (throughout the confluent monolayer, not only at the free edge) occurred after a shorter delay (0.25 vs. 2.0 h) and then five times faster than to Calu-3 cells, indicating that the time course of P. aeruginosa cytotoxicity may be limited by the rate of gaining access through tight junctions and that this occurred faster in low Rtthan in high Rtairway epithelia. Cytotoxicity appeared to occur in a sequential process that led first to a loss of fura 2 and a later uptake of propidium iodide. P. aeruginosa bound three times more frequently to regions between cells (tight junctions?) than to cell membranes of low RtCFT1 cells.

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Cellular biomechanics in the lung

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00141.2002 ◽

2002 ◽

Vol 283 (3) ◽

pp. L503-L509 ◽

Cited By ~ 39

Author(s):

Christopher M. Waters ◽

Peter H. S. Sporn ◽

Mingyao Liu ◽

Jeffrey J. Fredberg

Keyword(s):

Wound Healing ◽

Epithelial Cells ◽

Airway Hyperresponsiveness ◽

Mechanical Stretch ◽

Mechanical Deformation ◽

Airway Epithelial Cells ◽

Lung Epithelial Cells ◽

Stable Cell Line ◽

Normal Lung ◽

Mechanical Forces

Mechanical forces affect both the function and phenotype of cells in the lung. In this symposium, recent studies were presented that examined several aspects of biomechanics in lung cells and their relationship to disease. Wound healing and recovery from injury in the airways involve epithelial cell spreading and migration on a substrate that undergoes cyclic mechanical deformation; enhanced green fluorescent protein-actin was used in a stable cell line to examine cytoskeletal changes in airway epithelial cells during wound healing. Eosinophils migrate into the airways during asthmatic attacks and can also be exposed to cyclic mechanical deformation; cyclic mechanical stretch caused a decrease in leukotriene C4 synthesis that may be dependent on mechanotransduction mechanisms involving the production of reactive oxygen species. Recent studies have suggested that proinflammatory cytokines are increased in ventilator-induced lung injury and may be elevated by overdistention of the lung tissue; microarray analysis of human lung epithelial cells demonstrated that cyclic mechanical stretch alone profoundly affects gene expression. Finally, airway hyperresponsiveness is a basic feature of asthma, but the relationship between airway hyperresponsiveness and changes in airway smooth muscle (ASM) function remain unclear. New analysis of the behavior of the ASM cytoskeleton (CSK) suggests, however, that the CSK may behave as a glassy material and that glassy behavior may account for the extensive ASM plasticity and remodeling that contribute to airway hyperresponsiveness. Together, the presentations at this symposium demonstrated the remarkable and varied roles that mechanical forces may play in both normal lung physiology as well as pathophysiology.

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Overview of Cold Atmospheric Plasma in Wounds Treatment

Medical & Clinical Research ◽

10.33140/mcr.05.10.04 ◽

2020 ◽

Vol 5 (10) ◽

Keyword(s):

Wound Healing ◽

Skin Wound ◽

Atmospheric Plasma ◽

Active Components ◽

Negative Effects ◽

Skin Wound Healing ◽

Cold Atmospheric Plasma ◽

In Vivo Experiments

Cold atmospheric plasma (CAP), a room temperate ionised gas, known as the fourth state of matter is an ionised gas and can be produced from argon, helium, nitrogen, oxygen or air at atmospheric pressure and low temperatures. CAP has become a new promising way for many biomedical applications, such as disinfection, cancer treatment, root canal treatment, wound healing, and other medical applications. Among these applications, investigations of plasma for skin wound healing have gained huge success both in vitro and in vivo experiments without any known significant negative effects on healthy tissues. The development of CAP devices has led to novel therapeutic strategies in wound healing, tissue regeneration and skin infection management. CAP consists of a mixture of multitude of active components such as charged particles, electric field, UV radiation, and reactive gas species which can act synergistically. CAP has lately been recognized as an alternative approach in medicine for sterilization of wounds by its antiseptic effects and promotion of wound healing by stimulation of cell proliferation and migration of wound related skin cells. With respect to CAP applications in medicine, this review focuses particularly on the potential of CAP and the known molecular basis for this action. We summarize the available literature on the plasma devices developed for wound healing, the current in vivo and in vitro use of CAP, and the mechanism behind it as well as the biosafety issues.

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Basolateral K+ channels in airway epithelia. II. Role in Cl- secretion and evidence for two types of K+ channel

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1990.258.6.l343 ◽

1990 ◽

Vol 258 (6) ◽

pp. L343-L348 ◽

Cited By ~ 13

Author(s):

J. D. McCann ◽

M. J. Welsh

Keyword(s):

Epithelial Cells ◽

Time Course ◽

Basolateral Membrane ◽

Airway Epithelial Cells ◽

K Channel ◽

Airway Epithelial ◽

K Channels ◽

Cl Secretion ◽

Transient Component ◽

Permeable Supports

We previously described a Ca2(+)-activated K+ channel (KCLIC) in airway epithelial cells [J. D. McCann, J. Matsuda, M. Garcia, G. Kaczorowski, and M. J. Welsh. Am. J. Physiol 258 (Lung Cell. Mol. Physiol. 2): L334-L342, 1990]. To determine whether the KCLIC channel is a basolateral membrane channel and to understand its role in Cl- secretion, we studied airway epithelial cells grown on permeable supports. When cells were stimulated with A23187, charybdotoxin (ChTX) inhibited Cl- secretion and 86Rb efflux at the same concentrations, indicating that the KCLIC channel is required for Ca2(+)-stimulated Cl- secretion. We also investigated the function of K+ channels in adenosine 3',5'-cyclic monophosphate-stimulated secretion. Addition of isoproterenol caused a biphasic increase in Cl- secretion; the time course of the transient component correlated with the time course of the isoproterenol-induced increase in Ca2+ concentration [( Ca2+]c). ChTX inhibited the transient component, but not the prolonged component of secretion; Ba2+ inhibited the sustained component. These results suggest that when cells are grown on permeable supports isoproterenol-induced secretion depends on activation of two types of K+ channel: the KCLIC channel that is stimulated initially and a ChTX-insensitive K+ channel that is stimulated during sustained secretion. This conclusion was supported by measurement of 86Rb efflux from cell monolayers

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