scholarly journals The Role of Vitamin D and Vitamin D Receptor in Immunity toLeishmania majorInfection

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
James P. Whitcomb ◽  
Mary DeAgostino ◽  
Mark Ballentine ◽  
Jun Fu ◽  
Martin Tenniswood ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Responses ◽  
Vitamin D Receptor ◽  
Leishmania Major ◽  
Active Form ◽  
Wild Type ◽  
Vitamin D Signaling ◽  
Deficient Mice ◽  
Th 1

Vitamin D signaling modulates a variety of immune responses. Here, we assessed the role of vitamin D in immunity to experimental leishmaniasis infection in vitamin D receptor-deficient mice (VDRKO). We observed that VDRKO mice on a genetically resistant background have decreasedLeishmania major-induced lesion development compared to wild-type (WT) mice; additionally, parasite loads in infected dermis were significantly lower at the height of infection. Enzymatic depletion of the active form of vitamin D mimics the ablation of VDR resulting in an increased resistance toL. major. Conversely, VDRKO or vitamin D-deficient mice on the susceptible Th2-biased background had no change in susceptibility. These studies indicate vitamin D deficiency, either through the ablation of VDR or elimination of its ligand, 1,25D3, leads to an increase resistance toL. majorinfection but only in a host that is predisposed for Th-1 immune responses.

scholarly journals Vitamin D Signaling in Inflammation and Cancer: Molecular Mechanisms and Therapeutic Implications

Molecules ◽  
2020 ◽  
Vol 25 (14) ◽  
pp. 3219 ◽  
Author(s):  
Ahmed El-Sharkawy ◽  
Ahmed Malki
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Anticancer Agents ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Active Form ◽  
The Body ◽  
Skeletal Health ◽  
Therapeutic Benefits ◽  
Vitamin D Signaling

Vitamin D and its active metabolites are important nutrients for human skeletal health. UV irradiation of skin converts 7-dehydrocholesterol into vitamin D3, which metabolized in the liver and kidneys into its active form, 1α,25-dihydroxyvitamin D3. Apart from its classical role in calcium and phosphate regulation, scientists have shown that the vitamin D receptor is expressed in almost all tissues of the body, hence it has numerous biological effects. These includes fetal and adult homeostatic functions in development and differentiation of metabolic, epidermal, endocrine, neurological and immunological systems of the body. Moreover, the expression of vitamin D receptor in the majority of immune cells and the ability of these cells to actively metabolize 25(OH)D3 into its active form 1,25(OH)2D3 reinforces the important role of vitamin D signaling in maintaining a healthy immune system. In addition, several studies have showed that vitamin D has important regulatory roles of mechanisms controlling proliferation, differentiation and growth. The administration of vitamin D analogues or the active metabolite of vitamin D activates apoptotic pathways, has antiproliferative effects and inhibits angiogenesis. This review aims to provide an up-to-date overview on the effects of vitamin D and its receptor (VDR) in regulating inflammation, different cell death modalities and cancer. It also aims to investigate the possible therapeutic benefits of vitamin D and its analogues as anticancer agents.

scholarly journals The Emerging Role of Vitamin D and Vitamin D Receptor in Diabetic Nephropathy

2020 ◽  
Vol 2020 ◽  
pp. 1-8 ◽  
Author(s):  
Min Lei ◽  
Zhangsuo Liu ◽  
Jia Guo
Keyword(s):  
Vitamin D ◽  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Vitamin D Receptor ◽  
Interstitial Fibrosis ◽  
Microvascular Complications ◽  
Active Form ◽  
Nuclear Hormone Receptor ◽  
Protective Effects

Diabetic nephropathy (DN), one of the most common and severe microvascular complications of diabetes mellitus (DM), is an important risk factor for DM patient’s death. Nowadays, DN has become the leading cause of end-stage renal disease (ESRD) in most countries without effective therapeutic methods. Recently, the renoprotective effects mediated by vitamin D (VD) and vitamin D receptor (VDR) have been evidenced. VD, a kind of steroid with the active form 1,25(OH)2D3, has been known for the crucial roles in the modulation of serum calcium and phosphorus concentrations. It exerts important functions by binding with its receptor VDR.VDR, a transcription factor located at chromosome 12 containing 9 exons, is one of the nonsteroid nuclear hormone receptor superfamily, which participates in transcriptional regulation of genes in tissue- and cell-specific ways. Increasing evidences have demonstrated that VD/VDR signaling pathway possesses a variety of kidney-protective effects in DN patients, such as antiproteinuria, antifibrosis, anti-inflammatory, and preventing podocyte damage. Although there are many studies on the role of the VD/VDR signaling pathway in DN, the effects and mechanisms still need to be further explained. This review summarized the multiple roles of VD/VDR in podocyte injury, tubule lesions, interstitial fibrosis, and inflammation, as well as the clinical applications about DN to explore much more and effective therapeutic methods for DN.

scholarly journals Functional Vitamin D Receptor (VDR) in the T-Tubules of Cardiac Myocytes: VDR Knockout Cardiomyocyte Contractility

Endocrinology ◽  
2007 ◽  
Vol 149 (2) ◽  
pp. 558-564 ◽  
Author(s):  
Daniel X. Tishkoff ◽  
Karl A. Nibbelink ◽  
Kristina H. Holmberg ◽  
Loredana Dandu ◽  
Robert U. Simpson
Keyword(s):  
Signal Transduction ◽  
Vitamin D ◽  
Cardiac Myocytes ◽  
Vitamin D Receptor ◽  
Cardiac Myocyte ◽  
Radioligand Binding ◽  
Active Form ◽  
Heart Cells ◽  
Wild Type ◽  
T Tubules

We have previously shown that the active form of vitamin D, 1,25 dihydroxyvitamin D3 [1,25(OH)2D3], has both genomic and rapid nongenomic effects in heart cells; however, the subcellular localization of the vitamin D receptor (VDR) in heart has not been studied. Here we show that in adult rat cardiac myocytes the VDR is primarily localized to the t-tubule. Using immunofluorescence and Western blot analysis, we show that the VDR is closely associated with known t-tubule proteins. Radioligand binding assays using 3H-labeled 1,25(OH)2D3 demonstrate that a t-tubule membrane fraction isolated from homogenized rat ventricles contains a 1,25(OH)2D3-binding activity similar to the classic VDR. For the first time, we show that cardiac myocytes isolated from VDR knockout mice show accelerated rates of contraction and relaxation as compared with wild type and that 1,25(OH)2D3 directly affects contractility in the wild-type but not the knockout cardiac myocyte. Moreover, we observed that acute (5 min) exposure to 1,25(OH)2D3 altered the rate of relaxation. A receptor localized to t-tubules in the heart is ideally positioned to exert an immediate effect on signal transduction mediators and ion channels. This novel discovery is fundamentally important in understanding 1,25(OH)2D3 signal transduction in heart cells and provides further evidence that the VDR plays a role in heart structure and function.

scholarly journals Macrophage secretion of miR-106b-5p causes renin-dependent hypertension

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
J. Oh ◽  
S. J. Matkovich ◽  
A. E. Riek ◽  
S. M. Bindom ◽  
J. S. Shao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Vitamin D ◽  
Endoplasmic Reticulum ◽  
Vitamin D Receptor ◽  
Conditional Knockout ◽  
Macrophage Infiltration ◽  
Wild Type ◽  
Induced Hypertension ◽  
Vitamin D Signaling ◽  
Inflammatory Macrophage

Abstract Myeloid cells are known mediators of hypertension, but their role in initiating renin-induced hypertension has not been studied. Vitamin D deficiency causes pro-inflammatory macrophage infiltration in metabolic tissues and is linked to renin-mediated hypertension. We tested the hypothesis that impaired vitamin D signaling in macrophages causes hypertension using conditional knockout of the myeloid vitamin D receptor in mice (KODMAC). These mice develop renin-dependent hypertension due to macrophage infiltration of the vasculature and direct activation of renal juxtaglomerular (JG) cell renin production. Induction of endoplasmic reticulum stress in knockout macrophages increases miR-106b-5p secretion, which stimulates JG cell renin production via repression of transcription factors E2f1 and Pde3b. Moreover, in wild-type recipient mice of KODMAC/miR106b−/− bone marrow, knockout of miR-106b-5p prevents the hypertension and JG cell renin production induced by KODMAC macrophages, suggesting myeloid-specific, miR-106b-5p-dependent effects. These findings confirm macrophage miR-106b-5p secretion from impaired vitamin D receptor signaling causes inflammation-induced hypertension.

Intestinal and renal adaptation to a low-Pi diet of type II NaPi cotransporters in vitamin D receptor- and 1αOHase-deficient mice

2005 ◽  
Vol 288 (2) ◽  
pp. C429-C434 ◽  
Author(s):  
Paola Capuano ◽  
Tamara Radanovic ◽  
Carsten A. Wagner ◽  
Desa Bacic ◽  
Shigeaki Kato ◽  
...  
Keyword(s):  
Vitamin D ◽  
Small Intestine ◽  
Vitamin D Receptor ◽  
Transepithelial Transport ◽  
Wild Type ◽  
Hydroxyvitamin D ◽  
Renal Adaptation ◽  
In The Wild ◽  
25 Hydroxyvitamin D ◽  
Deficient Mice

Intake of a low-phosphate diet stimulates transepithelial transport of Pi in small intestine as well as in renal proximal tubules. In both organs, this is paralleled by a change in the abundance of the apically localized NaPi cotransporters NaPi type IIa (NaPi-IIa) and NaPi type IIb (NaPi-IIb), respectively. Low-Pi diet, via stimulation of the activity of the renal 25-hydroxyvitamin-D3-1α-hydroxylase (1αOHase), leads to an increase in the level of 1,25-dihydroxy-vitamin D3 [1,25(OH)2D]. Regulation of the intestinal absorption of Pi and the abundance of NaPi-IIb by 1,25(OH)2D has been supposed to involve the vitamin D receptor (VDR). In this study, we investigated the adaptation to a low-Pi diet of NaPi-IIb in small intestine as well as NaPi-IIa in kidneys of either VDR- or 1αOHase-deficient mice. In both mouse models, upregulation by a low-Pi diet of the NaPi cotransporters NaPi-IIa and NaPi-IIb was normal, i.e., similar to that observed in the wild types. Also, in small intestines of VDR- and 1αOHase-deficient mice, the same changes in NaPi-IIb mRNA found in wild-type mice were observed. On the basis of the results, we conclude that the regulation of NaPi cotransport in small intestine (via NaPi-IIb) and kidney (via NaPi-IIa) by low dietary intake of Pi cannot be explained by the 1,25(OH)2D-VDR axis.

scholarly journals Synergistic Activation of the Prolactin Promoter by Vitamin D Receptor and GHF-1: Role of the Coactivators, CREB-Binding Protein and Steroid Hormone Receptor Coactivator-1 (SRC-1)

1999 ◽  
Vol 13 (7) ◽  
pp. 1141-1154 ◽  
Author(s):  
Ana I. Castillo ◽  
Ana M. Jimenez-Lara ◽  
Rosa M. Tolon ◽  
Ana Aranda
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Hormone Receptor ◽  
Binding Protein ◽  
Steroid Hormone ◽  
Steroid Hormone Receptor ◽  
Creb Binding Protein ◽  
Wild Type ◽  
Prl Gene

Abstract PRL gene expression is dependent on the presence of the pituitary-specific transcription factor GHF-1/Pit-1, which is transcribed in a highly restricted manner in cells of the anterior pituitary. In pituitary GH3 cells, vitamin D increases the levels of PRL transcripts and stimulates the PRL promoter. We have analyzed the role of GHF-1 and of the vitamin D receptor (VDR) to confer vitamin D responsiveness to the PRL promoter. For this purpose we have used nonpituitary HeLa cells, which do not express GHF-1. We found that VDR activates the PRL promoter both in a ligand-dependent and -independent manner through a sequence located between positions− 45/−27 in the proximal 5′-flanking region. This sequence also confers VDR and vitamin D responsiveness to a heterologous promoter. In the context of the PRL gene, VDR requires the presence of GHF-1 to activate the promoter. Truncation of the last 12 C-terminal amino acids of VDR, which contain the ligand-dependent activation function (AF2), abolishes regulation by vitamin D, suggesting that binding of coactivators to this region mediates ligand-dependent stimulation of the PRL promoter by the receptor. Indeed, expression of the coactivators, steroid hormone receptor coactivator-1 (SRC-1) and CREB-binding protein (CBP), significantly enhances the stimulatory effect of vitamin D mediated by the wild-type VDR but not by the AF2 mutant receptor. Furthermore, CBP also increases the activation of the PRL promoter by GHF-1 and the ligand-independent activation by both wild-type and mutant VDR.

scholarly journals Normal T and B Cell Responses Against SARS-CoV-2 in a Family With a Non-Functional Vitamin D Receptor: A Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Martin Kongsbak-Wismann ◽  
Fatima A. H. Al-Jaberi ◽  
Jonas Damgård Schmidt ◽  
Mustafa Ghanizada ◽  
Cecilie Bo Hansen ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune Response ◽  
General Population ◽  
Vitamin D Receptor ◽  
Adaptive Immune Response ◽  
Cell Responses ◽  
Adaptive Immune ◽  
Vitamin D Signaling ◽  
The Impact

The coronavirus disease 2019 (COVID-19) pandemic has severely impacted daily life all over the world. Any measures to slow down the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and to decrease disease severity are highly requested. Recent studies have reported inverse correlations between plasma levels of vitamin D and susceptibility to SARS-CoV-2 infection and COVID-19 severity. Therefore, it has been proposed to supplement the general population with vitamin D to reduce the impact of COVID-19. However, by studying the course of COVID-19 and the immune response against SARS-CoV-2 in a family with a mutated, non-functional vitamin D receptor, we here demonstrate that vitamin D signaling was dispensable for mounting an efficient adaptive immune response against SARS-CoV-2 in this family. Although these observations might not directly be transferred to the general population, they question a central role of vitamin D in the generation of adaptive immunity against SARS-CoV-2.

scholarly journals The role of vitamin D in autoimmune diseases: could sex make the difference?

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maria Luisa Dupuis ◽  
Maria Teresa Pagano ◽  
Marina Pierdominici ◽  
Elena Ortona
Keyword(s):  
Vitamin D ◽  
Autoimmune Diseases ◽  
Vitamin D Receptor ◽  
Immune Modulation ◽  
Current Knowledge ◽  
Active Form ◽  
Adaptive Immune System ◽  
Sex And Gender ◽  
Mediated Effects

AbstractOver the last decades, a central role for vitamin D in immune modulation has been well established. The active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with vitamin D receptor, exerts different activities on the innate and adaptive immune system, among which suppression of inflammation and promotion of tolerogenic responses. Vitamin D insufficiency has been linked to autoimmune disorders that commonly display significant differences between females and males due to genetic, epigenetic, hormonal, and environmental factors. Notably, a number of studies recently showed a cross-talk between vitamin D and the sex hormone estrogen. Estrogen-mediated effects on immune response may favor a Th1 profile or a Th2 profile, depending on hormone concentration. Thus, estrogen-mediated effects appear to be variable on autoimmunity depending on its concentration but also on the pathogenic mechanisms underlying the different autoimmune diseases (i.e., Th1- or Th2-mediated diseases). Notably, estrogen has been demonstrated to enhance vitamin D function favoring its accumulation, and increasing the expression of vitamin D receptor, thus resulting in a more potent anti-inflammatory response in females than males. On the other hand, vitamin D has been shown to downregulate in immune cells the expression of aromatase, which converts testosterone to estrogen, leading to a decrease in estrogen level. Overall, available data allow us to hypothesize a higher protective effect of vitamin D-based therapeutic approaches in women, at least in fertile age, than in men. Future studies are needed to expand current knowledge on the immunomodulatory role of vitamin D in a sex and gender perspective, paving the way to a more personalized therapeutic approach in autoimmune diseases.

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