STIMULATION VERSUS INHIBITION OF KERATINOCYTE GROWTH BY 1,25-DIHYDROXYVITAMIN D-3 - DEPENDENCE ON CELL-CULTURE CONDITIONS

1,25-Dihydroxyvitamin D-3 (1,25[OH]D-2(3)) inhibits proliferation of k eratinocytes in vitro and psoriatic epidermal cells in vivo and is con sidered to be a negative regulator of keratinocyte growth. It has been recently observed, however, that 1,25(OH)(2)D-3 and its active analog s stimulate epidermal proliferation after topical application in mice. In this study we show that 1,25(OH)(2)D-3, depending on the culture c onditions, can either stimulate or inhibit DNA synthesis in human kera tinocytes. In cells cultured with 0.15 mM calcium in the absence or wi th low levels (0.1 ng/ml) of epidermal growth factor, exposure to 10(- 11)-10(-6) M 1,25(OH)(2)D-3 imposed cell cycle block in the late G1 ph ase. When keratinocytes were cultured in the presence of high extracel lular calcium concentration (1.8 mM), 1,25(OH)(2)D-3 in concentrations of 10(-11)-10(-9) M stimulated cell growth by increasing the proporti on of cells entering S phase. 1,25(OH)(2)D-3 also stimulated growth of keratinocytes cultured in low calcium concentrations when the cells w ere previously suspended for a short time in a semisolid medium, Growt h stimulation was absent in the presence of the anti-E-cadherin antibo dy, which is known to inhibit calcium-dependent differentiation, These results suggest that keratinocytes committed to terminal differentiat ion by an elevation of calcium concentration or suspension in a semiso lid medium respond to 1,25(OH)(2)D-3 with an increase in DNA synthesis , In contrast, proliferating undifferentiated keratinocytes map be the main target for the anti-proliferative activity of 1,25(OH)(2)D-3.