title: Skin electroporation of a plasmid encoding hCAP-18/LL-37 host defense peptide promotes wound healing.
abstract: Host defense peptides, in particular LL-37, are emerging as potential therapeutics for promoting wound healing and inhibiting bacterial growth. However, effective delivery of the LL-37 peptide remains limiting. We hypothesized that skin-targeted electroporation of a plasmid encoding hCAP-18/LL-37 would promote the healing of wounds. The plasmid was efficiently delivered to full-thickness skin wounds by electroporation and it induced expression of LL-37 in the epithelium. It significantly accelerated reepithelialization of nondiabetic and diabetic wounds and caused a significant VEGFa and interleukin (IL)-6 induction. IL-6 was involved in LL-37-mediated keratinocyte migration in vitro and IL-6 neutralizing antibodies delivered to mice were able to suppress the wound healing activity of the hCAP-18/LL-37 plasmid. In a hindlimb ischemia model, electroporation of the hCAP-18/LL-37 plasmid increased blood perfusion, reduced muscular atrophy, and upregulated the angiogenic chemokines VEGFa and SDF-1a, and their receptors VEGF-R and CXCR-4. These findings demonstrate that a localized gene therapy with LL-37 is a promising approach for the treatment of wounds.
authors.affiliation: Department of Plastic, Reconstructive and Aesthetic Surgery, Handsurgery, Evangelisches Krankenhaus Oldenburg, European Medical School, Oldenburg, Germany.
authors.forename: Lars
authors.initials: L
authors.lastname: Steinstraesser
authors.affiliation: 1] Department of Plastic Surgery, Burn Center, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany [2] Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Martin C
authors.initials: MC
authors.lastname: Lam
authors.affiliation: Department of Plastic Surgery, Burn Center, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Jacobsen
authors.affiliation: Institut de Recherches Experimentales et Cliniques, Pole of Pharmacology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Paolo E
authors.initials: PE
authors.lastname: Porporato
authors.affiliation: Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Kiran Kumar
authors.initials: KK
authors.lastname: Chereddy
authors.affiliation: Department of Plastic Surgery, Burn Center, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Mustafa
authors.initials: M
authors.lastname: Becerikli
authors.affiliation: Institute of Pathology, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Ingo
authors.initials: I
authors.lastname: Stricker
authors.affiliation: Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Robert Ew
authors.initials: RE
authors.lastname: Hancock
authors.affiliation: Department of Plastic Surgery, Burn Center, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bochum, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Lehnhardt
authors.affiliation: Institut de Recherches Experimentales et Cliniques, Pole of Pharmacology, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Pierre
authors.initials: P
authors.lastname: Sonveaux
authors.affiliation: Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
authors.affiliation: Louvain Drug Research Institute, Pharmaceutics and Drug Delivery, Université catholique de Louvain, Brussels, Belgium.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Vandermeulen
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000008:administration & dosage / Q000235:genetics*; D002478:Cells, Cultured; D053672:Electrochemotherapy; D015316:Genetic Therapy; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D014945:Wound Healing / Q000235:genetics*; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins