Immune regulation of 1alpha-hydroxylase in murine peritoneal macrophages: unravelling the IFNgamma pathway.
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.
Stoffels
K
K
Laboratory for Experimental Medicine and Endocrinology (LEGENDO), University Hospital Gasthuisberg, Catholic University of Leuven, Onderwijs en Navorsing, Herestraat 49, B-3000 Leuven, Belgium.
Overbergh
L
L
Bouillon
R
R
Mathieu
C
C
D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050832:Interferon-Stimulated Gene Factor 3 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology* / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology*
D050856:Interferon Regulatory Factor-1; D050832:Interferon-Stimulated Gene Factor 3; C079868:gamma interferon activation factor; D007371:Interferon-gamma; D006899:Mixed Function Oxygenases