Effects of 1α,25-Dihydroxyvitamin D3 on Macrophage Colony-Stimulating Factor Production and Proliferation of Human Monocytic Cells

Abstract

Abstract1α-25-Dihydroxyvftamin D3 [1α,25(OH)2D3] stimulates the proliferation of human monocytes in vitro. In the present study, we investigated a possible role of macrophage colony-stimulating factor (M-CSF) in 1α,25(OH)2D3-induced proliferation of human circulating monocytes and the effects of 1α,25(OH)2D3 on M-CSF production by human monocytic cells. Both 1α,25(OH)2D3 and recombinant human M-CSF increased 2.5-fold the nucleus number of human circulating monocytes on day 6 of the culture. These effects were inhibited by antihuman M-CSF antibody as well as by anti-c-fms antibody, although these antibodies themselves did not affect the nucleus number when added to control culture. These results indicated that M-CSF is required for 1α,25(OH)2D3-stimulated monocyte proliferation. In addition, 1α,25(OH)2D3 stimulated M-CSF secretion from human circulating monocytes. Secretion and mRNA expression of M-CSF by 12-0-tetradecanoylphorbol-13-acetate (TPA)-treated THP-1 ceils (human monocytic leukemia cell line) and TPA-treated HL-60 ceils (human promyelocyte leukemia cell line) were also increased by 1α,25(OH)2D3. M-CSF secretion from TPA-treated THP-1 cells was increased by 1α,25(OH)2D3 in a dose-dependent and metabolite-specific manner. The present study demonstrates that 1α,25(OH)2D3 is a potent stimulator for M-CSF production by human monocytic cells and that the proliferative effect of 1α,25(OH)2D3 on human monocytes may be attributed, at least in part, to the stimulated secretion of M-CSF.