FK506 and cyclosporin A inhibit growth factor-stimulated human keratinocyte proliferation by blocking cells in the G0/G1 phases of the cell cycle.

FK506, a new immunosuppressive agent, is effective in treating patients with psoriasis. A major feature of psoriasis vulgaris is the hyperproliferation of keratinocytes together with inflammation. To determine the effect of FK506 or cyclosporin A (CsA) on the keratinocyte cell cycle, flow cytometry and the growth factor free normal human keratinocyte-arrested system were used to assess keratinocyte proliferation. FK506 and CsA inhibit keratinocyte proliferation induced by EGF, TGF-alpha or IL-6. The antiproliferative effects of FK506 and CsA directly correlated with blockade of the keratinocyte cell cycle at the G0/G1 phases. These findings might indicate that the effects of FK506 and CsA on proliferation of cultured normal human keratinocytes are probably related to direct effects on growth regulation of keratinocytes via EGF, TGF-alpha or IL-6 stimulation.