Cargando…

Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1

BACKGROUND: Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (sNAG) results in increased kinetics of wound closure in diabetic animal models, which is due in part to increased expression of several cytokines, growth factors, and innate immune activation. Defensins are also imp...

Descripción completa

Detalles Bibliográficos
Autores principales: Lindner, Haley Buff, Zhang, Aiguo, Eldridge, Juanita, Demcheva, Marina, Tsichilis, Philip, Seth, Arun, Vournakis, John, Muise-Helmericks, Robin C.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084735/
https://www.ncbi.nlm.nih.gov/pubmed/21559496
http://dx.doi.org/10.1371/journal.pone.0018996
_version_ 1782202541787840512
author Lindner, Haley Buff
Zhang, Aiguo
Eldridge, Juanita
Demcheva, Marina
Tsichilis, Philip
Seth, Arun
Vournakis, John
Muise-Helmericks, Robin C.
author_facet Lindner, Haley Buff
Zhang, Aiguo
Eldridge, Juanita
Demcheva, Marina
Tsichilis, Philip
Seth, Arun
Vournakis, John
Muise-Helmericks, Robin C.
author_sort Lindner, Haley Buff
collection PubMed
description BACKGROUND: Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (sNAG) results in increased kinetics of wound closure in diabetic animal models, which is due in part to increased expression of several cytokines, growth factors, and innate immune activation. Defensins are also important for wound healing and anti-microbial activities. Therefore, we tested whether sNAG nanofibers induce defensin expression resulting in bacterial clearance. METHODOLOGY: The role of sNAG in defensin expression was examined using immunofluoresence microscopy, pharmacological inhibition, and shRNA knockdown in vitro. The ability of sNAG treatment to induce defensin expression and bacterial clearance in WT and AKT1−/− mice was carried out using immunofluoresent microscopy and tissue gram staining. Neutralization, using an antibody directed against β-defensin 3, was utilized to determine if the antimicrobial properties of sNAG are dependent on the induction of defensin expression. CONCLUSIONS/FINDINGS: sNAG treatment causes increased expression of both α- and β-type defensins in endothelial cells and β-type defensins in keratinocytes. Pharmacological inhibition and shRNA knockdown implicates Akt1 in sNAG-dependent defensin expression in vitro, an activity also shown in an in vivo wound healing model. Importantly, sNAG treatment results in increased kinetics of wound closure in wild type animals. sNAG treatment decreases bacterial infection of cutaneous wounds infected with Staphylococcus aureus in wild type control animals but not in similarly treated Akt1 null animals. Furthermore, sNAG treatment of S. aureus infected wounds show an increased expression of β-defensin 3 which is required for sNAG-dependent bacterial clearance. Our findings suggest that Akt1 is involved in the regulation of defensin expression and the innate immune response important for bacterial clearance. Moreover, these findings support the use of sNAG nanofibers as a novel method for enhancing wound closure while simultaneously decreasing wound infection.
format Text
id pubmed-3084735
institution National Center for Biotechnology Information
language English
publishDate 2011
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-30847352011-05-10 Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1 Lindner, Haley Buff Zhang, Aiguo Eldridge, Juanita Demcheva, Marina Tsichilis, Philip Seth, Arun Vournakis, John Muise-Helmericks, Robin C. PLoS One Research Article BACKGROUND: Treatment of cutaneous wounds with poly-N-acetyl-glucosamine nanofibers (sNAG) results in increased kinetics of wound closure in diabetic animal models, which is due in part to increased expression of several cytokines, growth factors, and innate immune activation. Defensins are also important for wound healing and anti-microbial activities. Therefore, we tested whether sNAG nanofibers induce defensin expression resulting in bacterial clearance. METHODOLOGY: The role of sNAG in defensin expression was examined using immunofluoresence microscopy, pharmacological inhibition, and shRNA knockdown in vitro. The ability of sNAG treatment to induce defensin expression and bacterial clearance in WT and AKT1−/− mice was carried out using immunofluoresent microscopy and tissue gram staining. Neutralization, using an antibody directed against β-defensin 3, was utilized to determine if the antimicrobial properties of sNAG are dependent on the induction of defensin expression. CONCLUSIONS/FINDINGS: sNAG treatment causes increased expression of both α- and β-type defensins in endothelial cells and β-type defensins in keratinocytes. Pharmacological inhibition and shRNA knockdown implicates Akt1 in sNAG-dependent defensin expression in vitro, an activity also shown in an in vivo wound healing model. Importantly, sNAG treatment results in increased kinetics of wound closure in wild type animals. sNAG treatment decreases bacterial infection of cutaneous wounds infected with Staphylococcus aureus in wild type control animals but not in similarly treated Akt1 null animals. Furthermore, sNAG treatment of S. aureus infected wounds show an increased expression of β-defensin 3 which is required for sNAG-dependent bacterial clearance. Our findings suggest that Akt1 is involved in the regulation of defensin expression and the innate immune response important for bacterial clearance. Moreover, these findings support the use of sNAG nanofibers as a novel method for enhancing wound closure while simultaneously decreasing wound infection. Public Library of Science 2011-04-29 /pmc/articles/PMC3084735/ /pubmed/21559496 http://dx.doi.org/10.1371/journal.pone.0018996 Text en Lindner et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lindner, Haley Buff
Zhang, Aiguo
Eldridge, Juanita
Demcheva, Marina
Tsichilis, Philip
Seth, Arun
Vournakis, John
Muise-Helmericks, Robin C.
Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1
title Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1
title_full Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1
title_fullStr Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1
title_full_unstemmed Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1
title_short Anti-Bacterial Effects of Poly-N-Acetyl-Glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1
title_sort anti-bacterial effects of poly-n-acetyl-glucosamine nanofibers in cutaneous wound healing: requirement for akt1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3084735/
https://www.ncbi.nlm.nih.gov/pubmed/21559496
http://dx.doi.org/10.1371/journal.pone.0018996
work_keys_str_mv AT lindnerhaleybuff antibacterialeffectsofpolynacetylglucosaminenanofibersincutaneouswoundhealingrequirementforakt1
AT zhangaiguo antibacterialeffectsofpolynacetylglucosaminenanofibersincutaneouswoundhealingrequirementforakt1
AT eldridgejuanita antibacterialeffectsofpolynacetylglucosaminenanofibersincutaneouswoundhealingrequirementforakt1
AT demchevamarina antibacterialeffectsofpolynacetylglucosaminenanofibersincutaneouswoundhealingrequirementforakt1
AT tsichilisphilip antibacterialeffectsofpolynacetylglucosaminenanofibersincutaneouswoundhealingrequirementforakt1
AT setharun antibacterialeffectsofpolynacetylglucosaminenanofibersincutaneouswoundhealingrequirementforakt1
AT vournakisjohn antibacterialeffectsofpolynacetylglucosaminenanofibersincutaneouswoundhealingrequirementforakt1
AT muisehelmericksrobinc antibacterialeffectsofpolynacetylglucosaminenanofibersincutaneouswoundhealingrequirementforakt1