title: Wound healing and expression of antimicrobial peptides/polypeptides in human keratinocytes, a consequence of common growth factors.
abstract: In addition to acting as a physical barrier against microorganisms, the skin produces antimicrobial peptides and proteins. After wounding, growth factors are produced to stimulate the regeneration of tissue. The growth factor response ceases after regeneration of the tissue, when the physical barrier protecting against microbial infections is re-established. We found that the growth factors important in wound healing, insulin-like growth factor I and TGF-alpha, induce the expression of the antimicrobial peptides/polypeptides human cationic antimicrobial protein hCAP-18/LL-37, human beta-defensin 3, neutrophil gelatinase-associated lipocalin, and secretory leukocyte protease inhibitor in human keratinocytes. Both an individual and a synergistic effect of these growth factors were observed. These findings offer an explanation for the expression of these peptides/polypeptides in the skin disease psoriasis and in wound healing and define a host defense role for growth factors in wound healing.
authors.affiliation: Granulocyte Research Laboratory, Department of Hematology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. sorensen@ucla.edu
authors.forename: Ole E
authors.initials: OE
authors.lastname: Sørensen
authors.forename: Jack B
authors.initials: JB
authors.lastname: Cowland
authors.forename: Kim
authors.initials: K
authors.lastname: Theilgaard-Mönch
authors.forename: Lide
authors.initials: L
authors.lastname: Liu
authors.forename: Tomas
authors.initials: T
authors.lastname: Ganz
authors.forename: Niels
authors.initials: N
authors.lastname: Borregaard
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000890:Anti-Infective Agents / Q000378:metabolism*; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics; D054804:Cathelicidins; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D006133:Growth Substances / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism* / Q000382:microbiology*; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D009924:Organ Culture Techniques; D014176:Protein Biosynthesis; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger / Q000096:biosynthesis; D016211:Transforming Growth Factor alpha / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D014945:Wound Healing / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D023083:beta-Defensins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000209:Acute-Phase Proteins; D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D054804:Cathelicidins; D016207:Cytokines; C406407:DEFB1 protein, human; D006133:Growth Substances; D018836:Inflammation Mediators; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D023083:beta-Defensins; D016222:Fibroblast Growth Factor 2; D007334:Insulin-Like Growth Factor I