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.
Neveu
I
I
Institut National de la Santé et de la Recherche Médicale, Centre Hospitalier Régional et Universitaire, Angers, France.
Naveilhan
P
P
Menaa
C
C
Wion
D
D
Brachet
P
P
Garabédian
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D001921:Brain / Q000166:cytology* / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002117:Calcitriol / Q000096:biosynthesis*; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D005904:Glial Fibrillary Acidic Protein / Q000276:immunology / Q000378:metabolism; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins
D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; D008070:Lipopolysaccharides; D018167:Receptors, Calcitriol; D011994:Recombinant Proteins; D007371:Interferon-gamma; D002117:Calcitriol