Synthesis of 1,25-dihydroxyvitamin D3 by rat brain macrophages in vitro.

Cultured microglial cells were examined for their ability to metabolize 25-hydroxyvitamin D3 (25-(OH) D3). Upon exposure to lipopolysaccharide, microglial cells produced a vitamin D metabolite which comigrated with synthetic 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) in two different systems of high performance liquid chromatography. This metabolite had the same affinity as synthetic 1,25-(OH)2D3 for the chick intestinal 1,25-(OH)2D3 receptor. Lipopolysaccharide-stimulated microglial cells incubated with 3 nM of 25-(OH) D3 synthesized up to 5.76 fmol 1,25-(OH)2D3/8 x 10(5) cells/2 hr. Microglial cells stimulated for 48 hr with interferon-gamma also produced a significant amount of 1,25-(OH)2D3 (4.17 fmol/8 x 10(5) cells/2 hr). In contrast, levels of 1,25-(OH)2D3 produced by resting microglial cells were barely detectable. It is concluded that activated brain macrophages may be committed to synthesize 1,25-(OH)2D3 in vitro. This raises the possibility that activation of microglial cells in vivo may be followed by an increase in the level of 1,25-(OH)2D3 in the central nervous system (CNS). These results support the emerging concept that the brain constitutes a target tissue for vitamin D metabolites.