title: 1,25-dihydroxyvitamin D3 impairs NF-κB activation in human naïve B cells.
abstract: 1α,25-dihydroxyvitamin D(3) (calcitriol), the bioactive metabolite of vitamin D, modulates the activation and inhibits IgE production of anti-CD40 and IL-4 stimulated human peripheral B cells. Engagement of CD40 results in NF-κB p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-κB mediated activation of human naïve B cells. Naïve B cells were predominantly targeted by calcitriol in comparison with memory B cells as shown by pronounced induction of the VDR target gene cyp24a1. Vitamin D receptor activation resulted in a strongly reduced p105/p50 protein and mRNA expression in human naïve B cells. This effect is mediated by impaired nuclear translocation of p65 and consequently reduced binding of p65 to its binding site in the p105 promoter. Our data indicate that the vitamin D receptor reduces NF-κB activation by interference with NF-κB p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naïve B cells, namely by reducing CD40 signaling.
authors.affiliation: Allergie-Centrum-Charité, CCM, Klinik für Dermatologie und Allergologie, Charité - Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany. kerstin.hilt@charite.de
authors.forename: Kerstin
authors.initials: K
authors.lastname: Geldmeyer-Hilt
authors.forename: Guido
authors.initials: G
authors.lastname: Heine
authors.forename: Björn
authors.initials: B
authors.lastname: Hartmann
authors.forename: Ria
authors.initials: R
authors.lastname: Baumgrass
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
authors.forename: Margitta
authors.initials: M
authors.lastname: Worm
mesh_terms: D021581:Active Transport, Cell Nucleus; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002117:Calcitriol / Q000378:metabolism* / Q000494:pharmacology; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000037:antagonists & inhibitors / Q000378:metabolism; D011401:Promoter Regions, Genetic; D018167:Receptors, Calcitriol / Q000819:agonists / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D018167:Receptors, Calcitriol; D051996:Transcription Factor RelA; D002117:Calcitriol