Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor
Ole E. Sørensen, … , Artur Schmidtchen, Tomas Ganz
Ole E. Sørensen, … , Artur Schmidtchen, Tomas Ganz
Published July 3, 2006
Citation Information: J Clin Invest. 2006;116(7):1878-1885. https://doi.org/10.1172/JCI28422.
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Research Article Dermatology

Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor

Abstract

We found that sterile wounding of human skin induced epidermal expression of the antimicrobial (poly)peptides human β-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 β-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.

Authors

Ole E. Sørensen, Dharma R. Thapa, K. Markus Roupé, Erika V. Valore, Ulf Sjöbring, Alice A. Roberts, Artur Schmidtchen, Tomas Ganz

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Figure 1

Expression of hBD-3, NGAL, and SLPI in wounded human skin.

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Expression of hBD-3, NGAL, and SLPI in wounded human skin. Human skin wa...
Human skin was sliced into 1- × 10-mm slices and incubated for 0–4 days in culture. Each day, samples were processed for IHC or extracted for RNA or protein. (A) Northern blots of total RNA from whole skin. The blots were hybridized with probes for hBD-3, NGAL, SLPI, and G3PD. Graphs show the expression of hBD-3, NGAL, and SLPI normalized to the expression of G3PD mRNA. hBD-3, NGAL, and SLPI mRNA concentrations in the skin on day 4 were assigned the value 1. (B) Skin slices on days 0 and 4 with and without treatment with AG-1478 were stained for hBD-3, NGAL, and SLPI. Color was developed with fast red chromogen, and Harris hematoxylin was used for counterstaining. (C) The proteins extracted from both the wounded skin and the medium were analyzed by AU-PAGE and SDS-PAGE using synthetic hBD-3 as a standard and then blotted and probed with antibodies to hBD-3, NGAL, and SLPI. hBD-3 was only found in the skin. In contrast, NGAL and SLPI were only detected in the culture medium of the wounded skin. SLPI migrated as a double band around 14 kDa. This double band was not found in all samples tested and is probably due to proteolytic cleavage of SLPI during the preparation of this particular sample. AU-PAGE was used for detection of hBD-3 since this method is superior for examining small cationic peptides.