SYNTHESIS OF 1,25-DIHYDROXYVITAMIN D-3 BY RAT-BRAIN MACROPHAGES IN-VITRO

Cultured microglial cells were examined for their ability to metaboliz e 25-hydroxyvitamin D-3 (25-(OH)D-3). Upon exposure to lipopolysacchar ide, microglial cells produced a vitamin D metabolite which comigrated with synthetic 1,25-dihydroxyvitamin D-3 (1,25-(OH)(2)D-3) in two dif ferent systems of high performance liquid chromatography. This metabol ite had the same affinity as synthetic 1,25-(OH)(2)D-3 for the chick i ntestinal 1,25-(OH)(2)D-3 receptor. Lipopolysaccharide-stimulated micr oglial cells incubated with 3 nM of 25-(OH) D-3 synthesized up to 5.76 fmol 1,25-(OH)(2)D-3/8 x 10(5) cells/2 hr. Microglial cells stimulate d for 48 hr with interferon-gamma also produced a significant amount o f 1,25-(OH)(2)D-3 (4.17 fmol/8 x 10(5) cells/2 hr). In contrast, level s of 1,25-(OH)(2)D-3 produced by resting microglial cells were barely detectable. It is concluded that activated brain macrophages may be co mmitted to synthesize 1,25-(OH)(2)D-3 in vitro. This raises the possib ility that activation of microglial cells in vivo may be followed by a n increase in the level of 1,25-(OH)(2)D-3 in the central nervous syst em (CNS). These results support the emerging concept that the brain co nstitutes a target tissue for vitamin D metabolites. (C) 1994 Wiley-Li ss, Inc.