Article

Regulation of 25-hydroxyvitamin D3-1 alpha-hydroxylase and production of 1 alpha,25-dihydroxyvitamin D3 by human dendritic cells.

Department of Hematology and Oncology, University of Regensburg, Franz-Josef-Strauss-Allee 11, D-93042 Regensburg, Germany.
Blood (impact factor: 9.9). 12/2003; 102(9):3314-6. DOI:10.1182/blood-2002-11-3521 pp.3314-6
Source: PubMed

ABSTRACT 25-Hydroxyvitamin D3-1 alpha-hydroxylase (25(OH)D3-1 alpha-hydroxylase), the key enzyme of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) production, is expressed in monocyte-derived macrophages (MACs). Here we show for the first time constitutive expression of 25(OH)D3-1 alpha-hydroxylase in monocyte-derived dendritic cells (DCs), which was increased after stimulation with lipopolysaccharide (LPS). Accordingly, DCs showed low constitutive production of 1,25(OH)2D3, but activation by LPS increased 1,25(OH)2D3 synthesis. In addition, 25(OH)D3-1 alpha-hydroxylase expression was found in blood DCs but not in CD34+-derived DCs. Next we analyzed the functional consequences of these results. Addition of 1,25(OH)2D3 at concentrations comparable with those produced by DCs inhibited the allostimulatory potential of DCs during the early phase of DC differentiation. However, terminal differentiation decreased the responsiveness of DCs to 1,25(OH)2D3. In conclusion, DCs are able to produce 1,25(OH)2D3 especially following stimulation with LPS. Terminal maturation renders DCs unresponsive to the effects of 1,25(OH)2D3, but those cells are able to suppress the differentiation of their own precursor cells in a paracrine way through the production of 1,25(OH)2D3.

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Keywords

25(OH)D3-1 alpha-hydroxylase
 
25(OH)D3-1 alpha-hydroxylase expression
 
25-Hydroxyvitamin D3-1 alpha-hydroxylase
 
allostimulatory potential
 
CD34+-derived DCs
 
concentrations comparable
 
DCs inhibited
 
first time constitutive expression
 
functional consequences
 
key enzyme
 
low constitutive production
 
monocyte-derived dendritic cells
 
monocyte-derived macrophages
 
own precursor cells
 
stimulation
 
terminal differentiation
 
Terminal maturation renders DCs unresponsive