Regulation of 25-hydroxyvitamin d-1alpha-hydroxylase by IFNgamma in human monocytic THP1 cells

The Journal of Steroid Biochemistry and Molecular Biology
L OverberghC Mathieu

Abstract

1,25-DihydroxyVitamin D(3) (1,25(OH)(2)D(3)), a molecule with well-known actions in bone and mineral homeostasis, also plays a role in the immune system. Indeed, the receptor for 1,25(OH)(2)D(3) is found in most immune cells and important immunological effects have been described in vitro, reflected by its capacity to prevent autoimmunity and to prolong graft survival. The aim of this study was to elucidate the intracellular pathways used by the immune system to regulate 1,25(OH)(2)D(3) production. Therefore we studied the regulation of 25-hydroxyvitamin-D-1alpha-hydroxylase (1alpha hydroxylase) in THP1 cells by IFNgamma, demonstrating that its induction is highly dependent on the activation/differentiation by PMA and occurred at a late time point (140-fold at 72 h, P < 0.05). Complete inhibition with actinomycin D indicated that the observed induction was, at least in part, a transcriptional event. Dose-dependent inhibition with cycloheximide demonstrated that the induction was dependent on "de novo" protein synthesis, a finding that correlates with the late time point of up-regulation. The data presented indicate a role for 1,25(OH)(2)D(3), activated by 1alpha hydroxylase, as a late down-tapering signal in the immune cascade.

Citations

Dec 15, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kristina EdfeldtRobert L Modlin
Feb 10, 2007·The Journal of Clinical Investigation·Jürgen SchauberRichard L Gallo
Oct 9, 2008·The Journal of Steroid Biochemistry and Molecular Biology·Jia LiDorothy Teegarden
Jul 11, 2006·Journal of Photochemistry and Photobiology. B, Biology·Katleen VantieghemSiegfried Segaert

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