Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor.
We found that sterile wounding of human skin induced epidermal expression of the antimicrobial (poly)peptides human beta-defensin-3, neutrophil gelatinase-associated lipocalin, and secretory leukocyte protease inhibitor through activation of the epidermal growth factor receptor. After skin wounding, the receptor was activated by heparin-binding epidermal growth factor that was released by a metalloprotease-dependent mechanism. Activation of the epidermal growth factor receptor generated antimicrobial concentrations of human beta-defensin-3 and increased the activity of organotypic epidermal cultures against Staphylococcus aureus. These data demonstrate that sterile wounding initiates an innate immune response that increases resistance to overt infection and microbial colonization.
Sørensen
Ole E
OE
Section of Clinical and Experimental Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. Ole_E.Sorensen@med.lu.se
Thapa
Dharma R
DR
Roupé
K Markus
KM
Valore
Erika V
EV
Sjöbring
Ulf
U
Roberts
Alice A
AA
Schmidtchen
Artur
A
Ganz
Tomas
T
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins; D051379:Mice; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000276:immunology* / Q000293:injuries* / Q000378:metabolism; D015533:Transcriptional Activation; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism
D000209:Acute-Phase Proteins; D023181:Antimicrobial Cationic Peptides; C422950:DEFB103A protein, human; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016211:Transforming Growth Factor alpha; D023083:beta-Defensins; D004815:Epidermal Growth Factor; D066246:ErbB Receptors