UVB increases urokinase-type plasminogen activator receptor (uPAR) expression

Keratinocytes synthesize and secrete urokinase-type plasminogen activator, which binds to its specific receptor on keratinocytes. When bound to urokin ase-type plasminogen activator receptor, urokinase-type plasminogen activat or proteolytically converts surface bound plasminogen to plasmin, which in turn cleaves many extracellular components leading to pericellular proteoly sis. The activation of the urokinase system has been observed during re-epi thelialization of skin wounds and in lesions of the autoimmune blistering s kin disease pemphigus, As pemphigus is photoinducible, we investigated the effect of ultraviolet B on urokinase-type plasminogen activator and urokina se-type plasminogen activator receptor expression in the epidermal keratino cyte cell line A431, Ultraviolet B increased cellular and secreted urokinas e-type plasminogen activator protein (enzyme-Linked immunosorbent assay) an d urokinase-type plasminogen activator receptor cell surface expression (fl ow cytometry) 24 h postirradiation. Northern blot analysis indicated that u ltraviolet B increased urokinase-type plasminogen activator receptor mRNA, Compared with a more rapid mRNA induction by epidermal growth factor (maxim al after 4 h) the ultraviolet B response was maximal after 24 h and prolong ed up to 36 h. The mRNA induction was not dependent on protein synthesis as judged by cycloheximide incubation. Ultraviolet B did not influence urokin ase-type plasminogen activator receptor mRNA stability (actinomycin D incub ation). A transiently transfected chloramphenicol acetyltransferase-reporte r construct containing a -398/+51 urokinase-type plasminogen activator rece ptor promoter fragment was activated when cells were exposed to ultraviolet B, This induction was almost completely abolished by mutating a -182/-176 AP-1 binding sequence. Ultraviolet B increased the binding capacity at this AP-1 motif in electrophoretic mobility shift assays. These data identify a distinct transcriptional mechanism by which ultraviolet B induces urokinas e-type plasminogen activator receptor. The epidermal induction of component s of the proteolytic urokinase system by ultraviolet B may help explain the photoinducibility of pemphigus lesions.