Immunomodulatory potential of Nisin A with application in wound healing

Abstract

Antimicrobial peptides can have a dual role with both antimicrobial activity against a broad range of bacteria and immunomodulatory effect, making them attractive as therapeutic treatment of difficult wounds. Nisin A is widely known for its antimicrobial activity, and a preliminary study demonstrated that it increased wound closure, but the mechanism behind its effect is unknown. The aim of this study is to elucidate the wound healing potential of Nisin A and the mechanism behind. First, an epithelial and endothelial cell line, human keratinocyte (HaCaT) and human umbilical vein endothelial cell, were used to demonstrate migration and proliferation effects in vitro. From HaCaT cells and peripheral blood mononuclear cell, changes in cytokine levels were shown by quantitative polymerase chain reaction and enzyme‐linked immunosorbent assay. Second, the ex vivo porcine wound healing model was used to investigate the re‐epithelization potential of Nisin A. Finally, the model Galleria mellonella was used to confirm antimicrobial activity and to investigate potential immunomodulatory effects in vivo. Here, we demonstrated that Nisin A affected migration significantly of both human umbilical vein endothelial cell and HaCaT cells (p < 0.05) but not proliferation, potentially by decreasing the levels of proinflammatory cytokines tumor necrosis factor‐α, interleukin‐6, and interleukin‐8 (p < 0.001). Furthermore, Nisin A treatment diminished lipopolysaccharide‐induced tumor necrosis factor‐α levels from peripheral blood mononuclear cells and monocyte chemoattractant protein‐1 from HaCaT cells (p < 0.001). Furthermore, Nisin A did not affect proliferation ex vivo either but increased re‐epithelization of the porcine skin. Nisin A improved survival of G. mellonella significantly from Staphylococcus epidermidis (p < 0.001) but not from Escherichia coli, indicating that Nisin A did not help the larvae to survive the infection in a different than direct antimicrobial way. All together this makes Nisin A a potential treatment to use in wound healing, as it increases the mobility of skin cells, dampens the effect of lipopolysaccharide and proinflammatory cytokines, and decreases bacterial growth.

Bioengineered Nisin Derivative M17Q Has Enhanced Activity against Staphylococcus epidermidis

“…To date, nisin resistance has not been observed or reported in S. epidermidis strains. Alongside this, nisin A has also been found to promote wound healing, without any observable cytotoxic effects in mammalian cells when tested in animals [12,23,41]. This suggests that nisin A and other nisin derived peptides could be viable treatment options in the fight against and prevention of, medical device associated infections in the future.…”

Nisin loaded carbopol gel against Pseudomonas aeruginosa infected third‐degree burns: A therapeutic intervention

“…Mouritzen et al 38 evaluated in vitro and ex vivo wound healing potential of Nisin A using HaCaT, HUVEC cell lines and porcine skin and demonstrated that Nisin A can affect the process of wound healing by decreasing bacterial growth and modulating pro-inflammatory cytokines.…”

Bacteriocins: Potential for Human Health

“…Nisin has been reported to have a significant antiinflammatory effect in vitro and in vivo. Nisin A can increase the activity of human keratinocytes HaCaT, inhibit LPSinduced proinflammatory cytokine levels (TNF-α), and reduce bacterial growth, promoting wound healing [73]. Nisin Z inhibits S. agalactiae and S. aureus and leads to a significantly decreased milk somatic cell count in cows with mastitis, thus effectively relieving the symptoms of mastitis [74].…”