Contact allergens and sodium lauryl sulphate upregulate vascular endothelial growth factor in normal keratinocytes

In allergic and irritant contact dermatitis, keratinocytes are major target cells that can be activated to take part in local reactions by secreting soluble mediators. Among the growth factors produced by keratinocytes, vascular endothelial growth factor (VEGF) is a powerful inducer of permeability of endothelial cells, and is involved in inflammation. We determined whether different contact allergens, dinitrosulphobenzene (DNSB), para-phenylenediamine (pPD) and the metals nickel and chromium, as distinct from cobalt, which has been shown to mimic the effects of hypoxia, can modify the basal level of VEGF in normal human keratinocytes when tested at various, non-toxic concentrations. The effects of an irritant, sodium lauryl sulphate (SLS), and of hydrocortisone were also tested. Our results showed an intense dose-dependent upregulation of VEGF release by keratinocytes after treatments by metals, pPD and SLS. DNSB induced only a moderate increase of VEGF. Hydrocortisone reduced the basal level as well as the nickel-induced upregulation of VEGF. These findings suggest that contact allergens and irritants probably upregulate VEGF in keratinocytes by different mechanisms and may contribute directly to the microvascular hyperpermeability which characterizes both contact and irritant dermatitis.