Immunomodulatory potential of Nisin A with application in wound healing

Michelle V Mouritzen; Athina Andrea; Katrine Qvist; Steen S. Poulsen; Håvard Jenssen

doi:10.1111/wrr.12743

Immunomodulatory potential of Nisin A with application in wound healing

Michelle V Mouritzen, Athina Andrea, Katrine Qvist, Steen S. Poulsen, Håvard Jenssen

Endocrinology and Metabolism

7 Citations (Scopus)

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.

Original language	English
Journal	Wound Repair and Regeneration
Volume	27
Issue number	6
Pages (from-to)	650-660
ISSN	1067-1927
DOIs	https://doi.org/10.1111/wrr.12743
Publication status	Published - 1 Nov 2019

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title = "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.",

author = "Mouritzen, {Michelle V} and Athina Andrea and Katrine Qvist and Poulsen, {Steen S.} and H{\aa}vard Jenssen",

note = "{\textcopyright} 2019 by the Wound Healing Society.",

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T1 - Immunomodulatory potential of Nisin A with application in wound healing

AU - Mouritzen, Michelle V

AU - Andrea, Athina

AU - Qvist, Katrine

AU - Poulsen, Steen S.

AU - Jenssen, Håvard

PY - 2019/11/1

Y1 - 2019/11/1

N2 - 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.

AB - 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.

U2 - 10.1111/wrr.12743

DO - 10.1111/wrr.12743

M3 - Journal article

C2 - 31287619

SN - 1067-1927

VL - 27

SP - 650

EP - 660

JO - Wound Repair and Regeneration

JF - Wound Repair and Regeneration

IS - 6

ER -

Immunomodulatory potential of Nisin A with application in wound healing

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