Reduced folate carrier (RFC-1) gene expression in normal and psoriatic skin

Methotrexate is widely used in the treatment of severe psoriasis, However, little is currently known about the mechanisms underlying its therapeutic a ctivity in the skin. Methotrexate has been shown to be carried into cells t hrough the reduced folate carrier (RFC-1), The recent cloning and character ization of the human gene encoding this transmembranal carrier enabled us t o investigate RFC-1 gene expression in human skin. Biopsies were obtained f rom the skin of healthy and psoriatic volunteers. RNA extracted from these biopsies was analyzed by the reverse transcriptase-polymerase chain reactio n technique. While RFC-1 gene expression was barely detectable in the uninv olved skin of psoriatic patients and in the skin of healthy volunteers, hig h levels of RFC-1 transcripts were found in biopsies obtained from psoriati c plaques. To further investigate this pattern of gene expression, we studi ed skin biopsies by in situ hybridization with a labeled antisense riboprob e specific for the RFC-1 gene. The RFC-1 gene was found to be weakly expres sed in the epidermis, in biopsies obtained from the skin of healthy subject s as well as in those from the uninvolved skin of psoriatic patients. In co ntrast, in biopsies obtained from psoriatic plaques, high levels of RFC-1 g ene transcripts were found mostly in the spinous layer of the epidermis, Th ese results suggest the existence of a specific methotrexate carrier in the human epidermis, and may bear relevance to the cutaneous manifestations of methotrexate toxicity.