LL-37

How LL-37 is described to act.

LL-37 is the 37-residue carboxy-terminal peptide cleaved from human cathelicidin hCAP18, produced by neutrophils and by various epithelial cells. Solid-state NMR of site-specifically labelled peptide in oriented lipid bilayers places the amphipathic helix parallel to the membrane surface and supports a toroidal-pore model of bilayer disruption, ruling out barrel-stave and detergent-like mechanisms in those systems. Independently of direct membrane activity, LL-37 is chemotactic for human monocytes, neutrophils and T lymphocytes and mobilizes calcium through the G-protein-coupled formyl peptide receptor-like 1 (FPRL1). It also complexes extracellular self-DNA into a form that engages endosomal TLR9 in plasmacytoid dendritic cells.

Mechanistic descriptions summarize published in vitro and animal work. They are not a representation of efficacy or safety in any subject, and no administration guidance is given or implied.

In radial diffusion and broth microdilution assays LL-37 showed MICs below 10 microgram/mL against Pseudomonas aeruginosa, Salmonella typhimurium, Escherichia coli, Listeria monocytogenes, staphylococci and vancomycin-resistant enterococci even in media containing 100 mM NaCl, but methicillin-resistant S. aureus, Proteus mirabilis and Candida albicans were resistant at that salt concentration and susceptible only in low-salt media. Cathelicidin-deficient mice were more susceptible to invasive group A streptococcal skin infection than wild-type animals, establishing an in vivo requirement for the peptide family in that model. In psoriatic skin, LL-37 bound to self-DNA converts it into a trigger for type I interferon production by plasmacytoid dendritic cells, a mechanism framed as driving autoimmune inflammation rather than host protection. A phase IIb multicentric double-blind, randomized, placebo-controlled trial administered topical LL-37 alongside compression therapy to 148 patients with hard-to-heal venous leg ulcers and measured wound healing; efficacy analysis on the full study population did not identify any significant difference from placebo.

Sources & references

Cited literature is provided for scientific reference only and does not constitute a representation of efficacy or safety in any subject. All research findings presented are sourced from peer-reviewed journals and are provided for educational reference only.

1. 01
   Evaluation of LL-37 in healing of hard-to-heal venous leg ulcers: A multicentric prospective randomized placebo-controlled clinical trial

   Mahlapuu M, et al. · Wound Repair Regen, 2021

   PMID 34687253DOI 10.1111/wrr.12977

2. 02
   Plasmacytoid dendritic cells sense self-DNA coupled with antimicrobial peptide

   Lande R, et al. · Nature, 2007

   PMID 17873860DOI 10.1038/nature06116

3. 03
   Mechanism of lipid bilayer disruption by the human antimicrobial peptide, LL-37

   Henzler Wildman KA, et al. · Biochemistry, 2003

   PMID 12767238DOI 10.1021/bi0273563

4. 04
   Innate antimicrobial peptide protects the skin from invasive bacterial infection

   Nizet V, et al. · Nature, 2001

   PMID 11719807DOI 10.1038/35106587

5. 05
   LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells

   De Yang, et al. · J Exp Med, 2000

   PMID 11015447DOI 10.1084/jem.192.7.1069

6. 06
   Activities of LL-37, a cathelin-associated antimicrobial peptide of human neutrophils

   Turner J, et al. · Antimicrob Agents Chemother, 1998

   PMID 9736536DOI 10.1128/AAC.42.9.2206

Every entry links to its record at the publisher or on PubMed. Titles are reproduced exactly as published.