The human antimicrobial peptide LL37 promotes wound healing and prevents chronic wound inflammation

Wound healing is a complex process that is often disrupted by pathogens, like Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli. Wound infection by these bacteria can interfere with the inflammatory phase, a crucial step in wound repair, which may lead to chronic wound formation. Recently, with the challenge of antibiotic resistance, wound infection has become more difficult to treat. The human cathelicidin LL37 is known to have anti-microbial activity and to modulate inflammation. We therefore hypothesized that it may serve both as a natural antibiotic and an enhancer of wound healing. Therefore, this study was aimed at understanding the effects of LL37 in wound healing with special focus on the modulation of inflammatory responses. The antimicrobial effects of LL37 were assessed by measuring the minimal inhibitory and minimal bactericidal concentrations, and its ability to kill intracellular bacteria was conducted on HMEC cells and macrophages. Inflammation modulatory effects were studied by flow cytometry, enzyme-linked immunosorbent assays, qPCR and RNA sequencing. In vivo wound regeneration and inflammation were investigated with zebrafish larvae upon tail amputation. Our results show that LL37 exhibits potent bactericidal activity and that it protects cells from bacterial invasion, modulates inflammation, promotes cell proliferation and accelerates the wound healing process both in vitro and in vivo. Our findings show that LL37 has not only potent anti-bacterial activity, but also modulates wound inflammation during the wound healing process. On this basis, LL37 may be applied to develop new therapeutic avenues to promote wound healing and prevent chronic wounds.