Immune Regulation of 1alpha-hydroxylase in Murine Peritoneal Macrophages: Unravelling the IFNgamma Pathway

J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):567-71. doi: 10.1016/j.jsbmb.2006.12.091. Epub 2006 Dec 27.

Abstract

The activated form of vitamin D(3), 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), plays an important role in the immune system. Indeed, receptors for 1,25(OH)(2)D(3) are found on most immune cells, and 1alpha-hydroxylase, the enzyme responsible for final activation of vitamin D(3), is expressed by monocytes/macrophages, resulting in secretion of 1,25(OH)(2)D(3) after immune stimulation. We have previously shown that in murine peritoneal macrophages 1alpha-hydroxylase is highly regulated by immune signals such as IFNgamma and LPS. In the present study we made use of two different knock-out mouse models with disruptions in two key transcription factors in the IFNgamma-signalling cascade (STAT1alpha and IRF1), to evaluate their role in the regulation of 1alpha-hydroxylase. This was performed by culturing peritoneal macrophages from these knock-out mice in the presence of IFNgamma and LPS, and evaluating the impact of the absence of the respective transcription factors on 1alpha-hydroxylase mRNA expression by real-time RT-PCR. In addition also the mRNA expression profiles of the essential transcription factors STAT1alpha, IRF1 and C/EBPbeta were investigated. The data confirm a crucial role for STAT1alpha as well as for C/EBPbeta in the regulation of 1alpha-hydroxylase in monocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Cells, Cultured
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Interferon Regulatory Factor-1 / deficiency
  • Interferon Regulatory Factor-1 / genetics
  • Interferon Regulatory Factor-1 / metabolism
  • Interferon-Stimulated Gene Factor 3 / deficiency
  • Interferon-Stimulated Gene Factor 3 / genetics
  • Interferon-Stimulated Gene Factor 3 / metabolism
  • Interferon-gamma / immunology*
  • Interferon-gamma / metabolism*
  • Macrophages, Peritoneal / immunology*
  • Macrophages, Peritoneal / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mixed Function Oxygenases / genetics
  • Mixed Function Oxygenases / immunology*
  • Mixed Function Oxygenases / metabolism*
  • Promoter Regions, Genetic / genetics
  • Signal Transduction / immunology*

Substances

  • Interferon Regulatory Factor-1
  • Interferon-Stimulated Gene Factor 3
  • gamma interferon activation factor
  • Interferon-gamma
  • Mixed Function Oxygenases