LL-37 (Human Cathelicidin) vs VIP (Vasoactive Intestinal Peptide)

LL-37 (Human Cathelicidin)

LL-37 is a 37-residue peptide cleaved from hCAP18, the only human cathelicidin; its name refers to its two leading leucines and its length. It is made by neutrophils and by epithelial cells of the skin, gut and airways, and the gene that encodes it is regulated in part by vitamin D. Laboratory studies have examined its activity against bacteria, fungi and some viruses, and its signalling to host immune and epithelial cells. Its research record runs in two directions: it is studied as a host-defence molecule and also as a contributor to inflammatory skin conditions such as psoriasis and rosacea. Most published work is in vitro or in animals, and interventional human studies are few and small.

VIP (Vasoactive Intestinal Peptide)

VIP, or vasoactive intestinal peptide, is a 28-residue amidated neuropeptide found in central and peripheral neurons and in the gut wall. It belongs to the secretin–glucagon family and is most closely related to pituitary adenylate cyclase-activating polypeptide (PACAP), with which it shares receptors. First isolated from intestinal tissue and named for its action on blood vessels, it is now studied as a neurotransmitter, a smooth-muscle signal and a messenger between the nervous and immune systems. Most of the literature comes from cell, tissue and animal studies. Synthetic VIP has been examined in small human studies, including in pulmonary conditions, but it is cleared from the circulation within a few minutes, which complicates that work.

How LL-37 (Human Cathelicidin) acts

In dilute aqueous solution LL-37 is largely disordered; on contact with lipid membranes it has been reported to fold into an amphipathic α-helix. Its side chains give it a net charge of about +6 at neutral pH, which draws it to the negatively charged surfaces of bacterial membranes, and it is thought to permeabilise those membranes. It also binds bacterial lipopolysaccharide. On host cells it has been reported to act through several receptors, among them 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 have been reported to activate Toll-like receptor signalling in dendritic cells, a pathway examined in psoriasis research.

How VIP (Vasoactive Intestinal Peptide) acts

VIP binds two class B G-protein-coupled receptors, VPAC1 and VPAC2, with similar affinity, and binds the PACAP-preferring PAC1 receptor much more weakly. Both VPAC receptors couple mainly to Gs, raising cyclic AMP and activating protein kinase A, although coupling to other G proteins has been described. In immune cell cultures this signalling has been reported to alter cytokine production and T-cell differentiation. In the suprachiasmatic nucleus, mouse studies indicate that VIP acting at VPAC2 helps synchronise the neurons of the circadian clock. In smooth muscle preparations it has been examined as a relaxant signal.

The records side by side

• Type: LL-37 (Human Cathelicidin), Antimicrobial peptide (cathelicidin); VIP (Vasoactive Intestinal Peptide), Neuropeptide (vasoactive intestinal peptide)
• Length: LL-37 (Human Cathelicidin), 37 amino acids; VIP (Vasoactive Intestinal Peptide), 28 amino acids
• Molecular weight: LL-37 (Human Cathelicidin), 4493 g/mol; VIP (Vasoactive Intestinal Peptide), 3326.8 g/mol
• Molecular formula: LL-37 (Human Cathelicidin), C205H340N60O53; VIP (Vasoactive Intestinal Peptide), C147H237N43O43S

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.