Dexamethasone Enhances 1α,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription

Hidalgo, Alejandro A.; Deeb, Kristin K.; Pike, J. Wesley; Johnson, Candace S.; Trump, Donald L.

doi:10.1074/jbc.m111.244061

Cited by 60 publications

(51 citation statements)

References 55 publications

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“…To compare VDR-mediated transcriptional activity induced by inecalcitol or 1,25D 3 in SCC cells, a luciferase reporter assay was used, as previously described. 8 Cells were infected with an adenoviral vector that carries the luciferase reporter gene driven by the CYP24A1 promoter. Treatment with 1 or 10 nM inecalcitol produced significantly higher VDR-mediated transcription of the CYP24A1 promoter compared with the same concentrations of 1,25D 3 (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

Hidalgo

et al. 2013

Cell Cycle

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Section: Resultsmentioning

confidence: 99%

“…VDR-mediated transcription was assessed in the presence of 1,25D 3 or inecalcitol by using an adenovirus carrying the firefly luciferase gene driven by the CYP24A1 promoter, which contains two VDREs. 8,25 Luciferase reporter assay was performed as described previously.…”

Section: Discussionmentioning

confidence: 99%

Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

Hidalgo

et al. 2013

Cell Cycle

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“…In these settings, corticosteroids are being used to enhance these vitamin D effects and for their anticalcemic properties [27]. Corticosteroids are known to stimulate vitamin D receptor protein expression by increasing VDR transcription [28], through binding of steroids to glucocorticoid response elements located in the promoter of the VDR [29], thus enhancing vitamin D effects on cancer cells. These mechanisms will need to be verified in model systems relevant for asthma and allergies.…”

Section: Potential Mechanisms Of Synergy Between Vitamin D and Corticosmentioning

confidence: 99%

Vitamin D and corticosteroids in asthma: synergy, interaction and potential therapeutic effects

Litonjua¹

2013

Expert Review of Respiratory Medicine

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“…In this respect, at least four mechanisms are known to regulate 1, 25[OH] 2 D activity. These are production of the active 1α-hydroxylated hormone by CYP27B1 [11,31,36], generation of relatively inactive 24α-hydroxylated metabolites by the action of CYP24A1 [31], sequestration by vitamin D-binding protein (VDBP) [37] and expression levels of the VDR [38]. We were interested in the regulation of vitamin D modulation of DC function.…”

Section: Discussionmentioning

confidence: 99%

Regulation of CYP27B1 and CYP24A1 hydroxylases limits cell‐autonomous activation of vitamin D in dendritic cells

et al. 2014

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Keywords: CYP27B1 r CYP24A1 r DCs r Macrophages r Vitamin D Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionThe capacity of vitamin D metabolites to modulate macrophage and DC function has been subject to extensive research interest in light of the association of vitamin D deficiency with a broad spectrum of immunological and infectious diseases. This gives Correspondence: Dr. Mahdad Noursadeghi e-mail: m.noursadeghi@ucl.ac.uk way to the potential for vitamin D supplementation [1][2][3][4] or ex vivo conditioning of DCs with vitamin D for cell therapy strategies [5]. Vitamin D is synthesized from 7-dehydrocholesterol in the skin following exposure to ultraviolet B radiation and thermal isomerisation, or replenished by dietary intake. It is 25-hydroxylated in the liver to form 25-hydroxyvitamin D (25[OH]D), which is in * These authors contributed equally to this work. Results 25[OH]D is not functionally activated during monocyte differentiation to immature DCsWe first compared the activation of 25[OH]D during monocyte differentiation into macrophages and immature DCs. Conventional cell culture media in this model are vitamin D deficient (Fig. 1A) (Fig. 1B). This was also associated with upregulation of the prototypic vitamin D-inducible gene cathelicidin (CAMP) in macrophages (Fig. 1C) (Fig. 1C). Importantly, upregulation of DC-SIGN during monocyte differentiation to DCs was not affected by the presence of 1,25[OH] 2 D (Fig. 1D) DCs show time-dependent increase in activation of 25[OH]D independent of CYP27B1 expression levelsWe confirmed previous observations [16] that expression of the vitamin D-activating hydroxylase CYP27B1 is significantly lower in DCs compared with MDMs at both transcript and protein levels ( Fig. 2A and B). In contrast, vitamin D receptor (VDR) expression was higher in DCs than MDMs ( Fig. 2A). Taken together, these data further support the hypothesis that 25[OH]D has no effect on DCs in the experiments described above, because of a failure to generate 1,25[OH] 2 D rather than an inability to respond to 1,25[OH] 2 D. We also confirmed that 24-h stimulation of DCs with LPS significantly increases transcript and protein levels of CYP27B1 ( Fig. 2B and C (Fig. 2D). However, there was no concomitant upregulation of CAMP (Fig. 2C) . Monocytes are typically differentiated to DCs over 4-7 days, therefore we considered the possibility that time in culture may confound comparisons between different studies. Interestingly, we did find 25[OH]D-dependent upregulation of CAMP gene expression in DCs that increased with time after at least 6 days in culture (Fig. 2E). This was not associated with any significant time-dependent increase in CYP27B1 expression ( DCs express truncated CYP27B1 transcriptsWe found that LPS stimulation was able to upregulate DC expression of CYP27B1 transcript to levels higher than that in MDMs ( Figs. 2A and C). However, the expression of CYP27B1 protein remains much lower in DCs compared with ...

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Dexamethasone Enhances 1α,25-Dihydroxyvitamin D3 Effects by Increasing Vitamin D Receptor Transcription

Cited by 60 publications

References 55 publications

Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

Inecalcitol, an analog of 1,25D₃, displays enhanced antitumor activity through the induction of apoptosis in a squamous cell carcinoma model system

Vitamin D and corticosteroids in asthma: synergy, interaction and potential therapeutic effects

Regulation of CYP27B1 and CYP24A1 hydroxylases limits cell‐autonomous activation of vitamin D in dendritic cells

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