Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure.
Antimicrobial peptides are endogenous antibiotics that directly inactivate microorganisms and in addition have a variety of receptor-mediated functions. LL-37/hCAP-18 is the only cathelicidin found in humans and is involved in angiogenesis and regulation of the innate immune system. The aim of the present study was to characterize the role of the peptide LL-37 in the regulation of wound closure of the airway epithelium in the cell line NCI-H292 and primary airway epithelial cells. LL-37 stimulated healing of mechanically induced wounds in monolayers of the cell line and in differentiated primary airway epithelium. This effect was detectable at concentrations of 5 mug/ml in NCI-H292 and 1 mug/ml in primary 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. Inhibitor studies in the wound closure and proliferation assays indicated that the effects caused by LL-37 are mediated through epidermal growth factor receptor, a G protein-coupled receptor, and MAP/extracellular regulated kinase. In conclusion, LL-37 induces wound healing, proliferation, and migration of airway epithelial cells. The peptide is likely involved in the regulation of tissue homeostasis in the airways.
Shaykhiev
Renat
R
Hospital of the University of Marburg, Department of Internal Medicine, Division of Pulmonary Diseases, Philipps-Universtät Marburg, Marburg, Germany.
Beisswenger
Christoph
C
Kändler
Kerstin
K
Senske
Judith
J
Püchner
Annette
A
Damm
Thomas
T
Behr
Jürgen
J
Bals
Robert
R
D023181:Antimicrobial Cationic Peptides / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology / Q000633:toxicity; D001483:Base Sequence; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D018076:DNA, Complementary / Q000235:genetics; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D044042:Receptors, Formyl Peptide / Q000235:genetics; D018102:Receptors, Leukotriene B4; D044067:Receptors, Lipoxin / Q000235:genetics; D018048:Receptors, Purinergic P2 / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D054804:Cathelicidins
D023181:Antimicrobial Cationic Peptides; D018076:DNA, Complementary; C105101:FPR2 protein, human; C513240:LTB4R protein, human; D044042:Receptors, Formyl Peptide; D018102:Receptors, Leukotriene B4; D044067:Receptors, Lipoxin; D018048:Receptors, Purinergic P2; D054804:Cathelicidins