Effects of cold physical plasma on oral lichen planus: An in vitro study ( Effects of CAP on OLP )

Zhang

et al. 2022

Front. Cell Dev. Biol.

Oral lichen planus (OLP) is an immune-inflammatory disease mediated by T cells. Innate lymphoid cells (ILCs) constitute a novel family of immune cells that initially originate from common innate lymphoid progenitors. Termed “T cells counterparts,” ILCs play a prominent role in inflammatory-immune diseases. However, the characterization of ILCs and their related induced factors were unclear in OLP. In the present study, the phenotypic characteristics of ILCs and their correlation with inflammatory cytokines were explored in the peripheral blood of OLP patients and healthy controls. We found that the proportion of total ILCs was expanded in OLP and was positively correlated with disease severity. The highly skewed distribution of ILC subpopulations was notable in OLP. Specifically, the frequency of ILC1s was significantly increased, while that of ILC2s was significantly reduced in total ILCs of OLP, resulting in the markedly elevated ILC1/ILC2 ratio in OLP. Correspondingly, ILCs in OLP displayed high expression of T-bet but low expression of GATA3. In addition, the IFN-γ expression level was elevated in ILC1s, whereas the IL-4 expression level was decreased in ILC2s. Moreover, ILC-associated activators IL-12, IL-18, and IL-1β were upregulated in OLP plasma, with IL-12 and IL-1β both positively correlated with the ILC1/ILC2 ratio. Further in vitro stimulation tests indicated that OLP plasma remarkedly increased the ILC1/ILC2 ratio, especially that IL-12 and IL-1β tipped the balance between ILC1s and ILC2s toward ILC1s in total ILCs. Overall, elevated levels of IL-12 and IL-1β might act as environmental cues in tipping the balance of ILC1/ILC2 in the peripheral blood of OLP, contributing to the immune dysregulation in OLP.

Section: Discussionsupporting

confidence: 85%

The Tipped Balance of ILC1/ILC2 in Peripheral Blood of Oral Lichen Planus Is Related to Inflammatory Cytokines

Zhang

et al. 2022

Front. Cell Dev. Biol.

Oxidative Medicine and Cellular Longevity

“…Moreover, cold physical plasmas at tissue-tolerable temperatures of around 40°C are used therapeutically and directly on the body surfaces due to their antibacterial, anti-inflammatory, and wound healing properties [ 145 ]. Other promising fields of application are expected in plastic surgery, oral medicine, and ophthalmology [ 146 – 148 ]. Oncology is an emerging treatment modality with great potency to convey synergy in the multimodal concept of antitumor therapy [ 6 , 149 , 150 ].…”

Section: Plasma Medicinementioning

confidence: 99%

H2A.X Phosphorylation in Oxidative Stress and Risk Assessment in Plasma Medicine

Schütz

Stope²,

Bekeschus

2021

Self Cite

At serine139-phosphorylated gamma histone H2A.X (γH2A.X) has been established over the decades as sensitive evidence of radiation-induced DNA damage, especially DNA double-strand breaks (DSBs) in radiation biology. Therefore, γH2A.X has been considered a suitable marker for biomedical applications and a general indicator of direct DNA damage with other therapeutic agents, such as cold physical plasma. Medical plasma technology generates a partially ionized gas releasing a plethora of reactive oxygen and nitrogen species (ROS) simultaneously that have been used for therapeutic purposes such as wound healing and cancer treatment. The quantification of γH2A.X as a surrogate parameter of direct DNA damage has often been used to assess genotoxicity in plasma-treated cells, whereas no sustainable mutagenic potential of the medical plasma treatment could be identified despite H2A.X phosphorylation. However, phosphorylated H2A.X occurs during apoptosis, which is associated with exposure to cold plasma and ROS. This review summarizes the current understanding of γH2A.X induction and function in oxidative stress in general and plasma medicine in particular. Due to the progress towards understanding the mechanisms of H2A.X phosphorylation in the absence of DSB and ROS, observations of γH2A.X in medical fields should be carefully interpreted.

“…As such, gas plasma was found to support physiological wound healing [ 19 ] via exogenous exposure to therapeutic doses of ROS and subsequent ROS-induced signaling pathways, potentially driving paracrine effects [ 20 ]. Gas plasma-generated ROS such as superoxide radicals and nitric oxide [ 21 ] affect cell proliferation, migration, chemotaxis, apoptosis, and inflammatory gene and protein expression [ 18 , 22 , 23 ]. However, many factors are associated with tissue repair, which might contribute to the fact that chronic wounds still are a clinical problem.…”

Section: Introductionmentioning

confidence: 99%

Gas plasma-spurred wound healing is accompanied by regulation of focal adhesion, matrix remodeling, and tissue oxygenation

et al. 2021

Self Cite

In response to injury, efficient migration of skin cells to rapidly close the wound and restore barrier function requires a range of coordinated processes in cell spreading and migration. Gas plasma technology produces therapeutic reactive species that promote skin regeneration by driving proliferation and angiogenesis. However, the underlying molecular mechanisms regulating gas plasma-aided cell adhesion and matrix remodeling essential for wound closure remain elusive. Here, we combined in vitro analyses in primary dermal fibroblasts isolated from murine skin with in vivo studies in a murine wound model to demonstrate that gas plasma treatment changed phosphorylation of signaling molecules such as focal adhesion kinase and paxillin α in adhesion-associated complexes. In addition to cell spreading and migration, gas plasma exposure affected cell surface adhesion receptors (e.g., integrinα5β1, syndecan 4), structural proteins (e.g., vinculin, talin, actin), and transcription of genes associated with differentiation markers of fibroblasts-to-myofibroblasts and epithelial-to-mesenchymal transition, cellular protrusions, fibronectin fibrillogenesis, matrix metabolism, and matrix metalloproteinase activity. Finally, we documented that gas plasma exposure increased tissue oxygenation and skin perfusion during ROS-driven wound healing. Altogether, these results provide critical insights into the molecular machinery of gas plasma-assisted wound healing mechanisms.