FK506 AND CYCLOSPORINE-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 patient s with psoriasis. A. major feature of psoriasis vulgaris is the hyperp roliferation of keratinocytes together with inflammation. To determine the effect of FK506 or cyclosporin A (CsA) on the keratinocyte cell c ycle, flow cytometry and the growth factor free normal human keratinoc yte-arrested system were used to assess keratinocyte proliferation. FK 506 and CsA inhibit keratinocyte proliferation induced by EGF, TGF-alp ha or IL-6. The antiproliferative effects of FK506 and CsA directly co rrelated with blockade of the keratinocyte cell cycle at the G0/G1 pha ses. These findings might indicate that the effects of FK506 and CsA o n proliferation of cultured normal human keratinocytes are probably re lated to direct effects on growth regulation of keratinocytes via EGF, TGF-alpha or IL-6 stimulation.