Vitamin D(3) 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 RT-PCR. 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 1h 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.
Zhu
Kejian
K
Department of Dermatology, University of Kiel, Kiel, Germany.
Gläser
Regine
R
Mrowietz
Ulrich
U
D018949:Antigens, CD1 / Q000096:biosynthesis; D002454:Cell Differentiation; D002470:Cell Survival; D002478:Cells, Cultured; D002762:Cholecalciferol / Q000031:analogs & derivatives*; D003713:Dendritic Cells / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000431:Ethanol / Q000494:pharmacology; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D007700:Kinetics; D008024:Ligands; D018950:Lipopolysaccharide Receptors / Q000096:biosynthesis; D016173:Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D009000:Monocytes / Q000378:metabolism; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015854:Up-Regulation; D014807:Vitamin D / Q000378:metabolism
D018949:Antigens, CD1; C419393:CD1a antigen; D006684:HLA-DR Antigens; D008024:Ligands; D018950:Lipopolysaccharide Receptors; D012333:RNA, Messenger; D014807:Vitamin D; D002762:Cholecalciferol; D000431:Ethanol; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor