title: Wound healing activity of the human antimicrobial peptide LL37.
abstract: Antimicrobial peptides (AMPs) are part of the innate immune system and are generally defined as cationic, amphipathic peptides, with less than 50 amino acids, including multiple arginine and lysine residues. The human cathelicidin antimicrobial peptide LL37 can be found at different concentrations in many different cells, tissues and body fluids and has a broad spectrum of antimicrobial and immunomodulatory activities. The healing of wound is a complex process that involves different steps: hemostasis, inflammation, remodeling/granulation tissue formation and re-epithelialization. Inflammation and angiogenesis are two fundamental physiological conditions implicated in this process. We have recently developed a new method for the expression and purification of recombinant LL37. In this work, we show that the recombinant peptide P-LL37 with a N-terminus proline preserves its immunophysiological properties in vitro and in vivo. P-LL37 neutralized the activation of macrophages by lipopolysaccharide (LPS). Besides, the peptide induced proliferation, migration and tubule-like structures formation by endothelial cells. Wound healing experiments were performed in dexamethasone-treated mice to study the effect of LL37 on angiogenesis and wound regeneration. The topical application of synthetic and recombinant LL37 increased vascularization and re-epithelialization. Taken together, these results clearly demonstrate that LL37 may have a key role in wound regeneration through vascularization.
authors.affiliation: IBB, Institute of Biotechnology and Bioengineering, Centre of Biological Engineering, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
authors.forename: Reinaldo
authors.initials: R
authors.lastname: Ramos
authors.forename: João Pedro
authors.initials: JP
authors.lastname: Silva
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Rodrigues
authors.forename: Raquel
authors.initials: R
authors.lastname: Costa
authors.forename: Luísa
authors.initials: L
authors.lastname: Guardão
authors.forename: Fernando
authors.initials: F
authors.lastname: Schmitt
authors.forename: Raquel
authors.initials: R
authors.lastname: Soares
authors.forename: Manuel
authors.initials: M
authors.lastname: Vilanova
authors.forename: Lucília
authors.initials: L
authors.lastname: Domingues
authors.forename: Miguel
authors.initials: M
authors.lastname: Gama
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins / Q000737:chemistry / Q000494:pharmacology*; D002465:Cell Movement / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000009:adverse effects / Q000494:pharmacology; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D006097:Granulation Tissue / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008853:Microscopy; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology*; D017695:Soft Tissue Injuries / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D003907:Dexamethasone