Modulation of Epidermal Growth Factor Receptors in Psoriatic Lesions During Treatment with Topical EGF

Active psoriatic lesions have increased EGF/TGFα receptors, historically known as the EGF-R. This increase is due to their persistence into the outer parakeratotic layer as measured by autoradiography, immunohistochemistry, and mRNA assays. When psoriatic lesions in patients resolve due to therapy with different modalities the EDF-R persistently expressed in the outer layers of the epidermis either disappear or resume a basal location presumably due to receptor down regulation. To test whether EGF could down regulate EGF-R and biologically affect psoriatic epidermis split thickness skin grafts of active psoriatic lesions were sutured onto the dorsal surface of nude mice. After 3 weeks, the mice were treated daily for a 6 week period with placebo or 10 or 50μg/ml EGF. Immunostaining showed persistent EGF-R in all epidermal layers in the untreated, placebo and 10μg/ml EGF-treated groups. Those grafts receiving a high dose of EGF (50 μg/ml) showed either no immunoreactive EGF-R or faint basilar staining. As an additional check for functional activity of the EFG-R, an abundant substrate for this receptor, PLC-γ was also evaluated flowing EGF treatment. A similar distribution and modulation pattern following treatment were observed in the grafts immunostained for PLC—γ1, suggestion that exogenous EGF treatment affected metabolic pathway subsequent to ligand receptor binding. Morphologic alterations characteristic of regressing psoriatic phenotype (a decrease in acanthosis, thickness. and the resumption of the orthokeratotic mode of differentiation) were noted in those lesions receiving the 50μ/ml EGF treatment. This study indicters that persistent EGF-R in psoriasis vulgarism are biologically active in vivo and may serve a pivotal role in the regulation of psoriatic lesions