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

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.