The Human Endogenous Antimicrobial Peptide Ll-37 Stimulates Airway Epithelial Repair

Antimicrobial peptides are endogenous antibiotics that directly inactivate microorganisms and in addition have a variety of other biological functions. LL-37/hCAP-18, the only cathelicidin antimicrobial peptide found in humans, is involved in angiogenesis and regulation of the innate immune system. The aim of the present study was to characterize the role of LL-37 in the regulation of the repair processes of the airway epithelium using NCI-H292 cell line and primary bronchial epithelial cells (PBEC). LL-37 stimulated healing of mechanically wounded differentiated primary airway epithelium and NCI-H292 cell monolayers. This effect was detectable at concentrations of 5µg/ml in NCI-H292 and 1µg/ml in primary cells. At these concentrations, LL-37 was not toxic for airway epithelial cells. The effect of LL-37 on wound healing was dependent on the presence of serum. LL-37 induced cell proliferation and migration of NCI-H292 cells, as determined by chemotaxis and BrdU incorporation assays, respectively. Inhibitor studies in the wound closure and proliferation assays indicated that the effects caused by LL-37 are mediated through a complex signalling pathway involving epidermal growth factor receptor (EGFR), a G protein-coupled receptor (GPCR), and MAP/extracellular regulated kinase (MEK). In conclusion, LL-37 induces wound healing, migration and proliferation of airway epithelial cells. The peptide is likely involved in the regulation of tissue homeostasis in the airways.