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.

Genome-Wide Transcriptional Analysis of <b><i>Drosophila</i></b> Larvae Infected by Entomopathogenic Nematodes Shows Involvement of Complement, Recognition and Extracellular Matrix Proteins

“…Recent data regarding infections of adult flies with EPNs suggest that AMPs can be induced by bacteria-free (axenic) nematodes, most likely also as a part of wounding defense [8]. Notably, the mammalian AMP LL-37 contributes to wound healing [45] as part of its pleiotropic effects [46]. …”

Anti-Microbial Peptides and Their Speculative Role in Periodontitis

“…By activating antigen-presenting cells, it presents as a hemoattractant for immune cells, including monocytes, T cells, etc. There is a specific correlation amongst multiplication in LL-37 levels and periodontal inflammation [25][26][27][28]. It is also known to cause an elevation in mucosal thickness in the gingiva.…”

Antimicrobial Peptides in Host Defense: Functions Beyond Antimicrobial Activity

“…Wound healing occurs in three phases: an infl ammatory phase, a proliferative phase, and a maturational phase (Sinno and Prakash 2013 ), all involving multiple steps in hemostasis, infl ammation, remodeling, formation of granulation tissue, and reepithelialization (Ramos et al 2011 ). The process involves various cells like fi broblasts, keratinocytes, endothelial cells, growth factors, extracellular matrix components, and chemokines and cytokines.…”

“…Histatins and LL-37 induce fi broblast migration, HBD2 promotes keratinocyte migration (Niyonsaba et al 2007 ), and LL-37 induces human microvascular endothelial cell and human umbilical vein endothelial cell migration (Ramos et al 2011 ). Histatins and LL-37 also induce fi broblast proliferation, HBD2 increases keratinocyte proliferation (Niyonsaba et al 2007 ;Warnke et al 2013 ), and LL-37 induces human microvascular endothelial cell and human umbilical vein endothelial cell proliferation (Ramos et al 2011 ).…”

“…LL-37 stimulates angiogenesis (Nakatsuji and Gallo 2012 ) and induces the formation of tubule-like structures (Ramos et al 2011 ). Another cathelicidin CRAMP has angiogenic properties, too (Kurosaka et al 2005 ).…”