Vitamin D3 and analogues modulate the expression of CSF-1 and its receptor in human dendritic cells

The active vitamin D-3-metabolite 1,25(OH)(2)D-3 inhibits the interleukin 4/granulocyte-macrophage colony-stimulating factor (IL-4/GM-CSF)-induced differentiation of human monocytes into dendritic cells without altering survival. Colony-stimulating factor 1 (CSF-1) is an important survival factor for cells of the monocytic lineage. We therefore investigated whether the inhibitory activity of 1,25(OH)(2)D-3 is paralleled by a regulation of CSF-1 and its receptor. Purified human monocytes were cultured together with IL-4/GM-CSF in the presence of 1,25(OH)(2)D-3, its analogue tacalcitol, the low-affinity vitamin D receptor-ligand 24,25(OH)(2)D-3, or the solvent ethanol for up to 5 days. Expression of CSF-1, CSF-1R, and GM-CSF mRNA was measured by RTPCR. Protein secretion for CSF-1 was measured by ELISA, expression of CSF-1R by flow cytometry. The results showed that 1,25(OH)(2)D-3 and tacalcitol significantly up-regulated CSF-1 mRNA-expression and protein secretion in a dose-dependent manner. The effect of 1,25(OH)(2)D-3 occurred already after 1 h of pre-treatment. In contrast, CSF-1R mRNA- and cell surface-expression was down-regulated simultaneously. The solvent ethanol and 24,25(OH)(2)D-3 were without effect. GM-CSF mRNA expression was not modulated in 1,25(OH)(2)D-3-treated cells. These data point towards a distinct and specific regulation of CSF-1 and its receptor by 1,25(OH)(2)D-3 and its analogue tacalcitol in human monocytes which parallels the inhibition of differentiation into dendritic cells without altering survival. (C) 2002 Elsevier Science (USA). All rights reserved.