Reduced Expression of Cyclins and Proliferative Indices on the Psoriatic Epidermis after 12 Weeks of Oral Cyclosporin Therapy

ABSTRACT

Cell growth characterized by cell cycle progression is regulated by cyclin-dependent kinase (CDK). CDKs are activated by binding cyclins such as cyclin A, cyclin B, cyclin D1, and cyclin E. Proliferative indices such as Ki-67 and proliferative cell nuclear antigen (PCNA) are known to be correlated with the mitotic index and were reported to have increased in the lesional psoriatic skin in previous reports. In this study, we investigated the expression of cyclins and proliferative indices (cyclin A, cyclin B, cyclin D1, cyclin E, Ki-67, and PCNA) in the psoriatic epidermis before and after cyclosporin therapy (3mg/kg/day 12 wks). Cyclin A, Ki-67, and PCNA were 1+ to 2+ positive before treatment but showed positive staining in only a few cells after treatment. Cyclin B and cyclin E were also moderate-to-strongly positive before treatment and became only weakly positive after treatment. Cyclin D1 was expressed only in a few cells and was negative after treatment. Taken together, cyclosporin may have an anti-proliferative effect on keratinocytes which was demonstrated by reduction of the proliferative indices such as Ki-67 and PCNA. The mechanism of the anti-proliferative effect may be through the inhibition of the cell cycle progression. Cyclin A, cyclin B and cyclin E are amongst the targeted cell cycle modulators, whereas cyclin D1 seems to be less induced in the lesional psoriatic epidermis, both before and after cyclosporin therapy.