Synergistic Effect of 1,25-Dihydroxyvitamin D3 and Retinoic Acid in Inducing U937 Cell Differentiation

Abstract

We examined the effects of retinoic acid (RA), 1,25-dihy-droxyvitamin D3 (l, 25-(OH)2D3), and its synthetic analogue, 22-oxa-1.25-(OH)2D3, on differentiation of U937 cells by studying the cellular growth, surface marker expression and cytosolic free Ca2+ concentration ([Ca2+]i). RA inhibited cellular growth but did not induce expression of Mo2 (CD14), a monocyte/macrophage specific surface marker. To the contrary, l, 25-(OH)2D3 did not inhibit cellular growth, but increased CD 14-positive cells. Simultaneous addition of l, 25-(OH)2D3 and RA had no additive effect on cellular growth inhibition or CD 14 expression. With regard to [Ca2+]i? however, 5 days' incubation with either of them increased the basal [Ca2+]j level and induced U937 cells to respond to formyl-methionyl-leucyl-phenylalanine (FMLP). When the cells were incubated with both 10-6m RA and 10∼8m l, 25-(OH)2D3, basal [Ca2+]j was higher and FMLP caused a greater increase in [Ca2+]j than when only RA or l,25-(OH)2D3 was added. These data suggest that RA and1.25-(OH)2D3 induce monocytoid differentiation in U937 cells through different pathways and act synergistically in the differentiation process. © 1992, Center for Academic Publications Japan. All rights reserved.