Low-temperature Plasma Promotes Fibroblast Proliferation in Wound Healing by ROS-activated NF-κB Signaling Pathway

Abstract

Low-temperature plasma (LTP) has shown great promise in wound healing, although the underlying mechanism remains poorly understood. In the present study, an argon atmospheric pressure plasma jet was employed to treat L929 murine fibroblasts cultured in vitro and skin wounds in BALB/c mice. The in vitro analysis revealed that treatment of fibroblasts with LTP for 15 s resulted in a significant increase in cell proliferation, secretion of epidermal growth factor (EGF) and transforming growth factor-βi (TGF-βi), production of intracellular reactive oxygen species (ROS), and the percentage of cells in S phase, protein expression of phosphorylated p65 (P-p65) and cyclinD1, but a noted decrease in the protein expression of inhibitor kappa B (IκB). The in vitro experiments demonstrated that 30-s LTP treatment enhanced the number of fibroblasts and the ability of collagen synthesis, while 50-s treatment led to the opposite outcomes. These results suggested that LTP treatment promotes the fibroblast proliferation in wound healing by inducing the generation of ROS, upregulating the expression of P-p65, downregulating the expression of IκB, and activating the NF-κB signaling pathway and consequently altering cell cycle progression (increased DNA synthesis in S phage).

Activation of the Normal Human Skin Cells by a Portable Dielectric Barrier Discharge-Based Reaction-Discharge System of a Defined Gas Temperature

“…These results showed that He-DBD might stimulate the proliferation of the normal human skin cells, which are involved in the wound healing process. Similar results were obtained by other research groups, who observed the increased proliferation of the cells treated with He-DBD over the short time periods [17,65]. In comparison to the epidermal keratinocytes and dermal fibroblasts, which are relatively robust towards the CAPP treatments, our results showed that the endothelial cells were more sensitive to the direct He-DBD treatment.…”

Boletus aereus protects against acute alcohol-induced liver damage in the C57BL/6 mouse via regulating the oxidative stress-mediated NF-κB pathway

“…Meanwhile, NF-jB can activate the transcription of the CXCL13 gene (Garg et al 2017) and regulate the expression of PAI-1 and RBP4 (Swiatkowska et al 2002;Zhou et al 2016). Conversely, ROS can be produced by the degradation of IjB, resulting in the phosphorylation of p65 (Shi et al 2018), thereby inducing binding of NF-jB to target sequences in the nucleus encoding the production of inflammatory factors (Lingappan 2018). Alcoholinduced oxidative stress can lead to an increase in the levels of pro-inflammatory cytokines, such as TNF-a or IL-1b (Galicia-Moreno and Guti errez-Reyes 2014).…”

Comprehensive biomedical applications of low temperature plasmas

“…The in vitro study showed that LTP exposure for 30 s increased the number of fibroblasts and the ability of collagen synthesis, while the exposure for 50 s led to opposed outcomes. This outcome indicates that LTP stimulates wound healing related fibroblast proliferation by inducing the production of ROS, upregulating phosphorylated p65 expression, downregulating inhibitor kappa B expression, and activating the NF-κB signaling pathway, leading to an altered cell cycle progression, demonstrated by the augmented DNA synthesis in S phase [20].…”

“…The applications of plasmas in medicine have attracted interest in the medical research communities [11]. Plasma medicine applications include treatment of oral biofilm-related infections [12,13], treatment of wounds and skin diseases [19][20][21], assistance in cancer treatment [22][23][24], treatment of viruses infections (e.g. herpes simplex [25]); as well as, but not limited to, optimization of implants surfaces [26][27][28].…”