title: Monocyte-derived cells express CYP27A1 and convert vitamin D3 into its active metabolite.
abstract: CYP27A1 catalyses hydroxylations in the biosynthesis of bile acids and the bioactivation of vitamin D3. We investigated the expression of CYP27A1 in human monocytes, monocyte-derived macrophages, and dendritic cells on mRNA and protein levels as well as its enzymatic activity in comparison with the expression of CYP27B1 and CYP24A1. Macrophages showed a strong expression of CYP27A1, whereas monocytes and dendritic cells expressed low levels of CYP27A1 mRNA. Immunohistochemistry revealed CYP27A1 and CYP27B1 protein expression in macrophages. Accordingly, macrophages converted vitamin D3 into the active metabolite 1,25(OH)2D3. Dendritic cells also metabolized vitamin D3 although to a lesser extent. This could be due to the high expression of CYP24A1, the enzyme that degrades 25(OH)D3 and 1,25(OH)2D3. Our results show that macrophages and dendritic cells are capable to perform both hydroxylation steps of the vitamin D3 metabolism suggesting a possible role of local 1,25(OH)2D3 synthesis by myeloid cells in the skin and gut.
authors.affiliation: Department of Hematology and Oncology, University of Regensburg, Franz-Josef Strauss Allee 11, 93042 Regensburg, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Gottfried
authors.forename: Michael
authors.initials: M
authors.lastname: Rehli
authors.forename: Joachim
authors.initials: J
authors.lastname: Hahn
authors.forename: Ernst
authors.initials: E
authors.lastname: Holler
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: Marina
authors.initials: M
authors.lastname: Kreutz
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism; D045744:Cell Line, Tumor; D002762:Cholecalciferol / Q000378:metabolism*; D053493:Cholestanetriol 26-Monooxygenase; D003713:Dendritic Cells / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000096:biosynthesis* / Q000737:chemistry*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D012333:RNA, Messenger; D002762:Cholecalciferol; D013250:Steroid Hydroxylases; C506831:CYP27A1 protein, human; D053493:Cholestanetriol 26-Monooxygenase; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase