MODULATION OF CELL-GROWTH, DIFFERENTIATION, AND PRODUCTION OF INTERLEUKIN-3 BY 1-ALPHA,25-DIHYDROXYVITAMIN-D3 IN THE MURINE MYELOMONOCYTIC LEUKEMIA-CELL LINE WEHI-3

Abstract

The effect of 1.alpha.,25-dihydroxyvitamin D3 [1.alpha.,25(OH)2D3], the active form of vitamin D3, on the relation between cell growth and differentiation was examined in a murine myelomonocytic leukemia cell line WEHI-3 which is known to produce high levels of interleukin-3. 1.alpha.,25(OH)2D3 markedly inhibited proliferation of WEHI-3 cells in a time- and dose-dependent manner. Flow cytometric analysis of the cell cycle by a double staining method using fluorescein isothiocyanate-conjugated anti-bromodeoxyuridine and propidium iodide revealed that 1.alpha.,25(OH2)D3 increased the proportion and the number of cells accumulating in the G0-G1 phase and decreased those in the S phase. The phenotype of the surface antigens of the cells was of the T-cell lineage, but the cells became positive in macrophage-associated surface markers (Mac-1 and Ia) after treatment with 1.alpha.,25(OH)2D3. The vitamin induced phagocytic activity, appearance of Fc receptors, nitroblue tetrazolium-reducing activity, and nonspecific esterase activity, indicating that the vitamin induces the cells to differentiate into macrophages. Furthermore, 1.alpha.,25(OH)2D3 inhibited interleukin-3 production by the cells in a time- and dose-dependent manner. These results suggest that 1.alpha.,25(OH)2D3 inhibits proliferation of WEHI-3 cells by blocking transition of the cells from the G0-G1 to the S phase, resulting in induction of the G0-G1 arrested cells to differentiate into macrophages. The relation between the suppression by 1.alpha.,25(OH)2D3 of cell growth and interleukin-3 production remains to be elucidated in the future.