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Anti-bacterial effects of poly-N-acetyl-glucosamine nanofibers in cutaneous wound healing: requirement for Akt1.
PLoS One 2011; 6(4):e18996Plos

Abstract

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.

Authors+Show Affiliations

Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, South Carolina, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21559496

Citation

Lindner, Haley Buff, et al. "Anti-bacterial Effects of poly-N-acetyl-glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1." PloS One, vol. 6, no. 4, 2011, pp. e18996.
Lindner HB, Zhang A, Eldridge J, et al. Anti-bacterial effects of poly-N-acetyl-glucosamine nanofibers in cutaneous wound healing: requirement for Akt1. PLoS ONE. 2011;6(4):e18996.
Lindner, H. B., Zhang, A., Eldridge, J., Demcheva, M., Tsichlis, P., Tsichilis, P., ... Muise-Helmericks, R. C. (2011). Anti-bacterial effects of poly-N-acetyl-glucosamine nanofibers in cutaneous wound healing: requirement for Akt1. PloS One, 6(4), pp. e18996. doi:10.1371/journal.pone.0018996.
Lindner HB, et al. Anti-bacterial Effects of poly-N-acetyl-glucosamine Nanofibers in Cutaneous Wound Healing: Requirement for Akt1. PLoS ONE. 2011 Apr 29;6(4):e18996. PubMed PMID: 21559496.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-bacterial effects of poly-N-acetyl-glucosamine nanofibers in cutaneous wound healing: requirement for Akt1. AU - Lindner,Haley Buff, AU - Zhang,Aiguo, AU - Eldridge,Juanita, AU - Demcheva,Marina, AU - Tsichlis,Philip, AU - Tsichilis,Philip, AU - Seth,Arun, AU - Vournakis,John, AU - Muise-Helmericks,Robin C, Y1 - 2011/04/29/ PY - 2010/10/29/received PY - 2011/03/23/accepted PY - 2011/5/12/entrez PY - 2011/5/12/pubmed PY - 2011/12/13/medline SP - e18996 EP - e18996 JF - PloS one JO - PLoS ONE VL - 6 IS - 4 N2 - 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. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/21559496/Anti_bacterial_effects_of_poly_N_acetyl_glucosamine_nanofibers_in_cutaneous_wound_healing:_requirement_for_Akt1_ L2 - http://dx.plos.org/10.1371/journal.pone.0018996 DB - PRIME DP - Unbound Medicine ER -