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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

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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 3

Wound experiments in mice.

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Wound experiments in mice.
(A) Mice (n = 5) were wounded by sterile inci...
(A) Mice (n = 5) were wounded by sterile incisions. Two days later, the mice were sacrificed and the RNA was extracted from the wounded skin surrounding the cut. The mRNA expression of the murine orthologs of NGAL (24p3) and SLPI was analyzed by real-time qRT-PCR and shown as the difference in threshold cycles (Ct) between the gene of interest and β-actin as housekeeping gene control. The expression of 24p3 and SLPI in nonwounded skin was set to 0. Thus, the bars at day 2 depict the induction of SLPI and 24p3 as shown in changes of threshold cycles (ΔδCt). (B) Mouse skin was sliced into 1 × 10–mm slices and incubated for 2 days in culture (n = 4). RNA was extracted from the skin. The expression of 24p3 and SLPI was analyzed by real-time qRT-PCR. The mRNA expression is shown as the difference in threshold cycles between the gene of interest and β-actin as housekeeping gene control (ΔδCt). The expression of 24p3 and SLPI in nonwounded skin was set to 0 so that the bars at day 2 depict the induction of SLPI and 24p3.

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