Synthesis of 1,25‐dihydroxyvitamin D 3 by rat brain macrophages in vitro

Cultured microglial cells were examined for their ability to metabolize 25‐hydroxyvitamin D 3 (25‐(OH) D 3 ). Upon exposure to lipopolysaccharide, microglial cells produced a vitamin D metabolite which comigrated with synthetic 1,25‐dihydroxyvitamin D 3 (1,25‐(OH) 2 D 3 ) in two different systems of high performance liquid chromatography. This metabolite had the same affinity as synthetic 1,25‐(OH) 2 D 3 for the chick intestinal 1,25‐(OH) 2 D 3 receptor. Lipopolysaccharide‐stimulated microglial cells incubated with 3 nM of 25‐(OH) D 3 synthesized up to 5.76 fmol 1,25‐(OH) 2 D 3 /8 × 10 5 cells/2 hr. Microglial cells stimulated for 48 hr with interferon‐γ also produced a significant amount of 1,25‐(OH) 2 D 3 (4.17 fmol/8 × 10 5 cells/2 hr). In contrast, levels of 1,25‐(OH) 2 D 3 produced by resting microglial cells were barely detectable. It is concluded that activated brain macrophages may be committed to synthesize 1,25‐(OH) 2 D 3 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) 2 D 3 in the central nervous system (CNS). These results support the emerging concept that the brain constitutes a target tissue for vitamin D metabolites. © 1994 Wiley‐Liss, Inc.