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

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Abstract
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 × 105 cells/2 hr. Microglial cells stimulated for 48 hr with interferon‐γ also produced a significant amount of 1,25‐(OH)2D3 (4.17 fmol/8 × 105 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.