Scientific Reference
LL-37
Evidence profile: Preclinical, with limited uncontrolled human reports
LL-37 is the only cathelicidin that humans make. It is 37 residues long, which together with its two leading leucines gives the name, and it is cut from a precursor called hCAP18. Neutrophils produce it, as do epithelial cells of the skin, gut and airways, and the gene is partly under vitamin D control. Laboratory work has tested it against bacteria, fungi and some viruses and has followed its signals to host immune and epithelial cells. The research runs two ways: as a host-defence molecule, and as something that may contribute to inflammatory skin conditions such as psoriasis and rosacea. Mostly this is in vitro or animal work; interventional human studies are few and small.
Mechanism of Action
In dilute water LL-37 is mostly disordered, but on meeting lipid membranes it is reported to fold into an amphipathic alpha-helix. A net charge of roughly +6 at neutral pH attracts it to the negatively charged surface of bacterial membranes, which it is thought to permeabilise, and it also binds bacterial lipopolysaccharide. On host cells it has been reported to act through several receptors, including formyl peptide receptor 2 and the P2X7 purinergic receptor, and to transactivate the epidermal growth factor receptor in keratinocytes. Complexes of LL-37 with self-DNA or RNA are reported to trigger Toll-like receptor signalling in dendritic cells, a route examined in psoriasis research.
Molecular Information
- Type: Antimicrobial peptide (cathelicidin)
- Molecular weight: 4493 g/mol
- Molecular formula: C205H340N60O53
- CAS: 154947-66-7