Regulation of 25-hydroxyvitamin d-1alpha-hydroxylase by IFNgamma in human monocytic THP1 cells.
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.
Overbergh
Lut
L
Laboratory for Experimental Medicine and Endocrinology (LEGENDO), University Hospital Gasthuisberg, Catholic University of Leuven, Leuven, Belgium.
Stoffels
Katinka
K
Valckx
Dirk
D
Giulietti
Annapaula
A
Bouillon
Roger
R
Mathieu
Chantal
C
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D007371:Interferon-gamma; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase