Injury-induced innate immune response in human skin mediated by transactivation of the epidermal growth factor receptor
J. Clin. Invest. Ole E. Sørensen, et al. 116:1878 doi:10.1172/JCI28422 [Go to this article.]

Figure 7
Identification of EGFR ligand responsible for hBD-3 induction in wounded skin. (A) Skin slices were incubated with the metalloprotease inhibitor TAPI-1 or with the DMSO vehicle used to dissolve the TAPI-1. Expression of hBD-3 was analyzed by real-time qRT-PCR on days 0 and 4. The expression of hBD-3 at day 4 was set to 1. TAPI-1 inhibited the expression of hBD-3 compared with the DMSO vehicle (n = 3, P < 0.002). Mean and standard deviation are shown. (B) Skin slices (n = 4) were incubated with control antibodies or antibodies against TGF-α and HB-EGF. The expression of RNA was analyzed by real-time qRT-PCR and normalized to G3PD as housekeeping mRNA control. The expression of hBD-3 on day 4 in the presence of control antibodies was set to 1. Due to limited access to whole skin, not all of the inhibition experiments were carried out each time. HB-EGF antibodies significantly inhibited the expression of hBD-3 compared with control antibodies (P < 0.003). Mean and standard deviation are shown. (C) Skin slices were incubated with an analog of diphtheria toxin, CRM197 (n = 3). CRM197 associates with membrane-bound HB-EGF and prevents its proteolytic liberation. The expression of mRNA was analyzed by real-time qRT-PCR and normalized to the G3PD as housekeeping mRNA control. The expression of hBD-3 on day 4 was set to 1. CRM197 significantly inhibited the expression of hBD-3 compared with control antibodies (P < 0.03). Mean and standard deviation are shown.