Wound healing activity of the human antimicrobial peptide LL37

Reinaldo Ramos, João Pedro Silva, Ana Cristina Rodrigues, Raquel Costa, Luísa Guardão, Fernando Schmitt, Raquel Soares, Manuel Vilanova, Lucília Domingues, Miguel Gama*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

180 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1469-1476
Number of pages8
JournalPeptides
Volume32
Issue number7
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

Keywords

  • Angiogenesis
  • Antimicrobial peptide
  • LL37
  • Wound healing

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