1,25-dihydroxyvitamin D{sub 3} impairs NF-{kappa}B activation in human naive B cells

• Published in: Biochemical and biophysical research communications 2011-04, Vol.407 (4)
• Main Authors: Geldmeyer-Hilt, Kerstin, Heine, Guido, Deutsches Rheuma-Forschungszentrum Berlin, Chariteplatz 1, 10117 Berlin, Hartmann, Bjoern, Baumgrass, Ria, Radbruch, Andreas, Worm, Margitta
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; ASTHMA; CHROMATIN; GENES; MESSENGER-RNA; PROMOTERS; RECEPTORS; SWITCHES; TRANSLOCATION; VITAMIN D
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/J.BBRC.2011.03.078

Highlights: {yields} In naive B cells, VDR activation by calcitriol results in reduced NF-{kappa}B p105 and p50 protein expression. {yields} Ligating the VDR with calcitriol causes reduced nuclear translocation of NF-{kappa}B p65. {yields} Reduced nuclear amount of p65 after calcitriol incubation results in reduced binding of p65 on the p105 promoter. {yields} Thus, vitamin D receptor signaling may reduce or prevent activation of B cells and unwanted immune responses, e.g. in IgE dependent diseases such as allergic asthma. -- Abstract: 1{alpha},25-dihydroxyvitamin D{sub 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-{kappa}B p50 activation, which is essential for the class switch to IgE. Herein, we investigated by which mechanism calcitriol modulates NF-{kappa}B mediated activation of human naive B cells. Naive 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 naive 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-{kappa}B activation by interference with NF-{kappa}B p65 and p105. Thus, the vitamin D receptor inhibits costimulatory signal transduction in naive B cells, namely by reducing CD40 signaling.