Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption.

Vitamin D receptor-mediated suppression of RelB in antigen presenting cells: a paradigm for ligand-augmented negative transcriptional regulation.

Griffin MD, Dong X, Kumar R

Department of Internal Medicine, Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. griffin.matthew@mayo.edu

The immunological effects of vitamin D receptor (VDR) ligands include inhibition of dendritic cell (DC) maturation, suppression of T-helper type 1 (Th1) T-cell responses and facilitation of antigen-specific immune tolerance in vivo. While studying the molecular profile of DCs cultured in the presence of 1alpha,25(OH)D3 or synthetic D3 analogs we observed that expression of the NF-kappaB family member RelB, which plays an essential role in DC differentiation and maturation, is selectively suppressed by VDR ligands. Further in vitro and in vivo studies of VDR-mediated RelB suppression indicated that the mechanism for this effect involves direct binding of VDR/RXR alpha to a defined region of the relB promoter and assembly of a negative regulatory complex containing HDAC3, HDAC1, SMRT and, most likely, other factors. Interestingly, promoter engagement by VDR and HDAC3, but not the other identified components, is enhanced by addition of a VDR ligand and inhibited by a pro-maturational stimulus (LPS) that results in RelB upregulation. Promoter assays in a panel of cell lines suggest that the VDR ligand-dependent component of relB suppression may occur selectively in antigen presenting cells. Cell type-specific, ligand-enhanced negative transcriptional regulation represents a potentially novel paradigm for VDR-controlled genes. In this report we review the experimental data to support such a mechanism for relB regulation in DCs and present a model for the process.

Published 23 April 2007 in Arch Biochem Biophys, 460(2): 218-26.
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