Role of CD14 expression in the differentiation-apoptosis switch in human monocytic leukemia cells treated with 1 alpha,25-dihydroxyvitamin D-3 or dexamethasone in the presence of transforming growth factor beta

Transforming growth factor beta (TGF-beta) enhanced the growth-inhibitory a ctivities of dexamethasone (Dex) and 1 alpha,25-dihydroxyvitamin D-3 (VD3) on human monocytoid leukemia U937 cells. TGF-beta and VD3 synergistically i ncreased the expression of differentiation-associated markers such as the C D11b and CD14 antigens, whereas TGF-beta and Dex did not. On the other hand , TGF-beta and Dex synergistically increased the number of Apo2.7-positive cells, which represents the early stage of apoptosis, whereas TGF-beta and VD3 did not, suggesting that TGF-beta enhanced apoptosis with Dex and enhan ced monocytic differentiation with VD3. In the presence of TGF-beta, the re tinoblastoma susceptibility gene product, pRb, was synergistically dephosph orylated by Dex as well as VD3. TGF similarly enhanced the expression of th e p21(Waf1) gene in U937 cells treated with Dex and VD3. TGF-beta dose-depe ndently increased the expression of Bcl-2 and Bad and decreased the express ion of Bcl-X-L in U937 cells. Dex enhanced the down-regulation of Bcl-X-L e xpression in TGF-beta-treated cells, whereas VD3 blocked this down-regulati on of Bcl-X-L, However, the down-regulation of Bcl-X-L by treatment with th e antisense oligomer did not affect the apoptosis or differentiation of U93 7 cells. The apoptosis of CD14-positive cells was suppressed in the VD3 plu s TGF-beta-treated cultures. These results suggest that the expression of C D14 is involved in the survival of differentiated cells.