Gene Regulation by Vitamin D3

Carlberg, Carsten; Polly, Patsie

doi:10.1615/critreveukargeneexpr.v8.i1.20

Cited by 170 publications

(124 citation statements)

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“…Results in Fig. 4e show negligible effects of BXL-219 on TLR expression, whereas the mRNA encoding 25-hydroxyvitamin D-24-hydroxylase (CYP24), a primary vitamin Dresponsive gene (29), is up-regulated by ϳ100-fold, demonstrating the capacity of NOD islet cells to respond to VDR ligands. Similar results were obtained with NOD.SCID islets (data not shown).…”

Section: The Vitamin D Analog Bxl-219 Inhibits In Vitro Chemokine Promentioning

confidence: 97%

A Vitamin D Analog Down-Regulates Proinflammatory Chemokine Production by Pancreatic Islets Inhibiting T Cell Recruitment and Type 1 Diabetes Development

Giarratana

Penna

Amuchastegui

et al. 2004

The Journal of Immunology

168

112

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Type 1 diabetes (T1D) is an autoimmune disease characterized by leukocyte infiltration into the pancreatic islets, and we have previously shown that treatment of adult NOD mice with a vitamin D analog arrests the progression of insulitis, blocks Th1 cell infiltration into the pancreas, and markedly reduces T1D development, suggesting inhibition of chemokine production by islet cells. In this study, we show that all TLRs are expressed by mouse and human islet cells, and their engagement by pathogen-derived ligands markedly enhances proinflammatory chemokine production. The vitamin D analog significantly down-regulates in vitro and in vivo proinflammatory chemokine production by islet cells, inhibiting T cell recruitment into the pancreatic islets and T1D development. The inhibition of islet chemokine production in vivo persists after restimulation with TLR ligands and is associated with up-regulation of IκBα transcription, an inhibitor of NF-κB and with arrest of NF-κBp65 nuclear translocation, highlighting a novel mechanism of action exerted by vitamin D receptor ligands potentially relevant for the treatment of T1D and other autoimmune diseases.

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Section: The Vitamin D Analog Bxl-219 Inhibits In Vitro Chemokine Promentioning

confidence: 97%

A Vitamin D Analog Down-Regulates Proinflammatory Chemokine Production by Pancreatic Islets Inhibiting T Cell Recruitment and Type 1 Diabetes Development

Giarratana

Penna

Amuchastegui

et al. 2004

The Journal of Immunology

168

112

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“…The biological effects of 1,25(OH) 2 D 3 are mediated by the vitamin D receptor (VDR), a member of the superfamily of nuclear hormone receptors functioning as a agonist-activated transcription factor that binds to specific DNA sequence elements, vitamin D responsive elements, in vitamin D responsive genes and ultimately influences their rate of RNA polymerase II-mediated transcription (5).…”

mentioning

confidence: 99%

1,25-Dihydroxyvitamin D3 Selectively Modulates Tolerogenic Properties in Myeloid but Not Plasmacytoid Dendritic Cells

Penna

Amuchastegui

Giarratana

et al. 2007

The Journal of Immunology

315

229

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1,25-Dihydroxyvitamin D3 (1,25(OH)2D3) is an immunomodulatory agent inducing dendritic cells (DCs) to become tolerogenic. To further understand its mechanisms of action, we have examined the effects of 1,25(OH)2D3 on tolerogenic properties of blood myeloid (M-DCs) and plasmacytoid (P-DCs) human DC subsets. Exposure of M-DCs to 1,25(OH)2D3 up-regulated production of CCL22, a chemokine attracting regulatory T cells, whereas production of CCL17, the other CCR4 ligand, was reduced. 1,25(OH)2D3 also decreased IL-12p75 production by M-DCs, as expected, and inhibited CCR7 expression. 1,25(OH)2D3 treatment markedly increased CD4+ suppressor T cell activity while decreasing the capacity of M-DCs to induce Th1 cell development. Surprisingly, 1,25(OH)2D3 did not exert any discernible effect on tolerogenic properties of P-DCs, and even their high production of IFN-α was not modulated. In particular, the intrinsically high capacity of P-DCs to induce CD4+ suppressor T cells was unaffected by 1,25(OH)2D3. Both DC subsets expressed similar levels of the vitamin D receptor, and its ligation by 1,25(OH)2D3 similarly activated the primary response gene cyp24. Interestingly, 1,25(OH)2D3 inhibited NF-κB p65 phosphorylation and nuclear translocation in M-DCs but not P-DCs, suggesting a mechanism for the inability of 1,25(OH)2D3 to modulate tolerogenic properties in P-DCs.

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“…Most of the biological effects of calcitriol are elicited by the binding to VDR (Carlberg and Polly, 1998). Calcitriol is then inactivated by CYP24, a key metabolic enzyme, 9 the expression of which is regulated by VDR (Chen and DeLuca, 1995).…”

Section: Cyp24 and Vitamin D Receptor (Vdr)mentioning

confidence: 99%

MicroRNAs from biology to future pharmacotherapy: Regulation of cytochrome P450s and nuclear receptors

Nakajima

Yokoi

2011

Pharmacology & Therapeutics

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MicroRNAs (miRNAs) are a family of short, non-coding RNA whose final product is a 22-nucleotide functional RNA molecule. They regulate the expression of target genes by binding to complementary regions of transcripts to repress their translation or promote mRNA degradation. Since miRNAs regulate every aspect of cellular function, their dysregulation is associated with a variety of diseases including cancer, diabetes, and cardiovascular diseases.Therefore, miRNAs are now considered new therapeutic targets. However, the roles of miRNAs in the metabolism of xenobiotics and endobiotics have only recently been revealed.This review describes the current knowledge on the regulation of cytochrome P450s and nuclear receptors by miRNAs, the physiological and clinical significance. The miRNA expression is readily altered by chemicals, carcinogens, drugs, hormones, stress, or diseases, and the dysregulation of specific miRNAs might lead to changes in the drug metabolism potency or pharmacokinetics as well as pathophysiological changes. In the field of pharmacogenomics, the evaluation of miRNA-related polymorphisms would provide useful information for personalized medicine. Utilizing miRNAs opens a new era in the fields of drug metabolism and pharmacokinetics as well as toxicology.

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Gene Regulation by Vitamin D3

Cited by 170 publications

References 0 publications

A Vitamin D Analog Down-Regulates Proinflammatory Chemokine Production by Pancreatic Islets Inhibiting T Cell Recruitment and Type 1 Diabetes Development

A Vitamin D Analog Down-Regulates Proinflammatory Chemokine Production by Pancreatic Islets Inhibiting T Cell Recruitment and Type 1 Diabetes Development

1,25-Dihydroxyvitamin D3 Selectively Modulates Tolerogenic Properties in Myeloid but Not Plasmacytoid Dendritic Cells

MicroRNAs from biology to future pharmacotherapy: Regulation of cytochrome P450s and nuclear receptors

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