Down/regulation of epidermal growth factor receptors by dithranol.

Abstract

Dithranol is highly effective in the treatment of psoriasis, but the exact mechanism of action is not known. Since persistent expression of epidermal growth factor (EGF) receptors in psoriatic epidermis is assumed to have pathogenetic significance, we have studied the effects of dithranol on EGF binding to the human epidermal cell line SCL-II. After treatment of cells with dithranol or its therapeutically inactive oxidation product, danthrone, radioligand binding assays were performed with 125I-EGF. In therapeutically active concentrations (0.25-1 micrograms/ml) dithranol induced a decrease in EGF binding in a dose dependent manner. Danthrone was inactive. The inhibition occurred after a latency period of 6 h and reached its maximum at 24 h. At the concentration of 1 microgram/ml, the drug led to approximately a 70% decrease in the number of specific high-affinity EGF receptors (Bmax), whereas receptor affinity (Kd) showed no change. The down-regulation of EGF receptors on epidermal cells by dithranol may contribute to its antipsoriatic action.