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.
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(OH2D3 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.
D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007377:Interleukin-3 / Q000096:biosynthesis*; D007399:Interphase / Q000187:drug effects; D007951:Leukemia, Myeloid / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D051379:Mice
D000954:Antigens, Surface; D000949:Histocompatibility Antigens Class II; D007377:Interleukin-3; D002117:Calcitriol