LL-37 is a natural protein that helps the immune system. It keeps neutrophils (a type of white blood cell) alive by turning on certain survival signals, but it can also cause airway lining cells to die. This dual action means it could boost defenses against infections, but might also harm lung tissue under some conditions.

The human cathelicidin LL-37 is a cationic host defense peptide (antimicrobial peptide) expressed primarily by neutrophils and epithelial cells. This peptide, up-regulated under conditions of inflammation, has immunomodulatory and antimicrobial functions. We demonstrate that LL-37 is a potent inhibitor of human neutrophil apoptosis, signaling through P2X(7) receptors and G-protein-coupled receptors other than the formyl peptide receptor-like-1 molecule. This process involved modulation of Mcl-1 expression, inhibition of BID and procaspase-3 cleavage, and the activation of phosphatidylinositol-3 kinase but not the extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase pathway. In contrast to the inhibition of neutrophil apoptosis, LL-37 induced apoptosis in primary airway epithelial cells, demonstrating alternate consequences of LL-37-mediated modulation of apoptotic pathways in different human primary cells. We propose that these novel immunomodulatory properties of LL-37 contribute to peptide-mediated enhancement of innate host defenses against acute infection and are of considerable significance in the development of such peptides and their synthetic analogs as potential therapeutics for use against multiple antibiotic-resistant infectious diseases.