scholarly journals In Vitro and In Vivo Analysis of the Immune System of Vitamin D Receptor Knockout Mice

2001 ◽  
Vol 16 (11) ◽  
pp. 2057-2065 ◽  
Author(s):  
Chantal Mathieu ◽  
Evelyne Van Etten ◽  
Conny Gysemans ◽  
Brigitte Decallonne ◽  
Shigeaki Kato ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Vitamin D Receptor ◽  
Knockout Mice ◽  
In Vivo Analysis

scholarly journals 1,25-Dihydroxy-19-nor-vitamin D2, a Vitamin D Analog with Reduced Bone Resorbing Activity In Vitro

2000 ◽  
Vol 11 (10) ◽  
pp. 1857-1864
Author(s):  
L. SHANNON HOLLIDAY ◽  
STEPHEN L. GLUCK ◽  
EDUARDO SLATOPOLSKY ◽  
ALEX J. BROWN
Keyword(s):  
Vitamin D ◽  
Acid Phosphatase ◽  
Bone Resorption ◽  
Vitamin D Receptor ◽  
Intrinsic Activity ◽  
Tartrate Resistant Acid Phosphatase ◽  
Mouse Bone Marrow ◽  
Bone Resorbing Activity

Abstract. 1,25-Dihydroxy-19-nor-vitamin D2 (19-norD2), a new analog of 1,25(OH)2D3, suppresses parathyroid hormone in renal failure patients and in uremic rats but has less calcemic activity than 1,25(OH)2D3. Although 19-norD2 has high affinity for the vitamin D receptor and similar pharmacokinetics to those of 1,25(OH)2D3, it has much less bone resorbing activity in vivo. The intrinsic activity of 19-norD2 on osteoclastogenesis and activation of bone resorption in mouse bone marrow cultures was examined to determine the mechanism involved. 19-norD2 and 1,25(OH)2D3 (10 nM) were equivalent in stimulating the formation and maintenance of large multinucleated, tartrate-resistant acid phosphatase-positive cells. However, the amount of bone resorbed by osteoclasts stimulated by 10 nM 19-norD2, as measured by pit-forming assays, was reduced 62% compared with 10 nM 1,25(OH)2D3-stimulated osteoclasts (P < 0.05). This difference could not be attributed to enhanced catabolism or to downregulated vitamin D receptor. The rate of degradation of 19-norD2 in cultures was approximately 20% greater than 1,25(OH)2D3, not enough to account for the different effects on bone resorption. The VDR levels were identical in cultures that were treated with 19-norD2 and 1,25(OH)2D3. In summary, 19-norD2 is less effective than 1,25(OH)2D3 in stimulating mouse marrow osteoclasts to resorb bone. The reason for this difference is not clear but seems to involve the late maturation and/or activation of osteoclasts as the number of pits produced by each tartrate-resistant acid phosphatase-positive cell is reduced under stimulation by 19-norD2 compared with 1,25(OH)2D3.

scholarly journals The Vitamin D Receptor Is Present in Caveolae-Enriched Plasma Membranes and Binds 1α,25(OH)2-Vitamin D3in Vivo and in Vitro

2004 ◽  
Vol 18 (11) ◽  
pp. 2660-2671 ◽  
Author(s):  
Johanna A. Huhtakangas ◽  
Christopher J. Olivera ◽  
June E. Bishop ◽  
Laura P. Zanello ◽  
Anthony W. Norman
Keyword(s):  
Vitamin D ◽  
Plasma Membrane ◽  
Vitamin D Receptor ◽  
Plasma Membranes ◽  
Binding Protein ◽  
Kidney Tissue ◽  
Mouse Lung ◽  
Nuclear Fraction

Abstract The steroid hormone 1α,25(OH)2-vitamin D3 (1,25D) regulates gene transcription through a nuclear receptor [vitamin D receptor (VDR)] and initiation of rapid cellular responses through a putative plasma membrane-associated receptor (VDRmem). This study characterized the VDRmem present in a caveolae-enriched membrane fraction (CMF), a site of accumulation of signal transduction agents. Saturable and specific [3H]-1,25D binding in vitro was found in CMF of chick, rat, and mouse intestine; mouse lung and kidney; and human NB4 leukemia and rat ROS 17/2.8 osteoblast-like cells; in all cases the 1,25D KD binding dissociation constant = 1–3 nm. Our data collectively support the classical VDR being the VDRmem in caveolae: 1) VDR antibody immunoreactivity was detected in CMF of all tissues tested; 2) competitive binding of [3H]-1,25D by eight analogs of 1,25D was significantly correlated between nuclei and CMF (r2 = 0.95) but not between vitamin D binding protein (has a different ligand binding specificity) and CMF; 3) confocal immunofluorescence microscopy of ROS 17/2.8 cells showed VDR in close association with the caveolae marker protein, caveolin-1, in the plasma membrane region; 4) in vivo 1,25D pretreatment reduced in vitro [3H]-1,25D binding by 30% in chick and rat intestinal CMF demonstrating in vivo occupancy of the CMF receptor by 1,25D; and 5) comparison of [3H]-1,25D binding in VDR KO and WT mouse kidney tissue showed 85% reduction in VDR KO CMF and 95% reduction in VDR KO nuclear fraction. This study supports the presence of VDR as the 1,25D-binding protein associated with plasma membrane caveolae.

The calcimimetic R-568 increases vitamin D receptor expression in rat parathyroid glands

2007 ◽  
Vol 292 (5) ◽  
pp. F1390-F1395 ◽  
Author(s):  
M. E. Rodriguez ◽  
Y. Almaden ◽  
S. Cañadillas ◽  
A. Canalejo ◽  
E. Siendones ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Parathyroid Tissue ◽  
Receptor Expression ◽  
Parathyroid Glands ◽  
In Vivo Studies ◽  
Control Treatment ◽  
Maximum Increase

We previously demonstrated that extracellular calcium regulates vitamin D receptor (VDR) expression by parathyroid cells. Since the calcimimetic R-568 potentiates the effects of calcium on the calcium-sensing receptor, it was hypothesized that administration of R-568 may result in increased VDR expression in parathyroid tissue. In vitro studies of the effect of R-568 on VDR mRNA and protein were conducted in cultures of whole rat parathyroid glands and human hyperplastic parathyroid glands. In vivo studies in Wistar rats examined the effect of R-568 and calcitriol alone and in combination. Incubation of rat parathyroid glands in vitro with R-568 (0.001–1 μM) resulted in a dose-dependent decrease in parathyroid hormone (PTH) secretion and an increase in VDR expression (mean ± SE). Incubation in 1 mM calcium + 0.001 μM R-568 elicited an increase in VDR mRNA (306 ± 46%) similar to the maximum increase detected with 1.5 mM calcium (330 ± 42%). In vivo, VDR mRNA was increased after administration of R-568 (168 ± 9%, P < 0.001 vs. control) or calcitriol (198 ± 16%, P < 0.001 vs. control). Treatment with R-568 also increased VDR protein in normal rat parathyroid glands and in human parathyroid glands with diffuse, but not nodular, hyperplasia. In conclusion, the present study shows that the calcimimetic R-568 exerts a stimulatory effect on VDR expression in the parathyroid glands of study models and provides additional evidence for the use of calcimimetics in the treatment of secondary hyperparathyroidism.

scholarly journals Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 789 ◽  
Author(s):  
Mattia Bellan ◽  
Laura Andreoli ◽  
Chiara Mele ◽  
Pier Paolo Sainaghi ◽  
Cristina Rigamonti ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Autoimmune Diseases ◽  
Convincing Evidence ◽  
In Vivo Studies ◽  
Human Immune System ◽  
Therapeutic Implications ◽  
Wide Range

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

Role of Vitamin D Receptor in the Lithocholic Acid-Mediated CYP3A Induction in Vitro and in Vivo

2008 ◽  
Vol 36 (10) ◽  
pp. 2058-2063 ◽  
Author(s):  
Tsutomu Matsubara ◽  
Kouichi Yoshinari ◽  
Kazunobu Aoyama ◽  
Mika Sugawara ◽  
Yuji Sekiya ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Lithocholic Acid

scholarly journals Vitamin D receptor pathway is required for probiotic protection in colitis

2015 ◽  
Vol 309 (5) ◽  
pp. G341-G349 ◽  
Author(s):  
Shaoping Wu ◽  
Sonia Yoon ◽  
Yong-Guo Zhang ◽  
Rong Lu ◽  
Yinglin Xia ◽  
...  
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Knockout Mice ◽  
Target Genes ◽  
Lactobacillus Rhamnosus ◽  
Luciferase Reporter ◽  
Transcriptional Level ◽  
Probiotic Treatment

Low expression of vitamin D receptor (VDR) and dysfunction of vitamin D/VDR signaling are reported in patients with inflammatory bowel disease (IBD); therefore, restoration of VDR function to control inflammation in IBD is desirable. Probiotics have been used in the treatment of IBD. However, the role of probiotics in the modulation of VDR signaling to effectively reduce inflammation is unknown. We identified a novel role of probiotics in activating VDR activity, thus inhibiting inflammation, using cell models and VDR knockout mice. We found that the probiotics Lactobacillus rhamnosus strain GG (LGG) and Lactobacillus plantarum (LP) increased VDR protein expression in both mouse and human intestinal epithelial cells. Using the VDR luciferase reporter vector, we detected increased transcriptional activity of VDR after probiotic treatment. Probiotics increased the expression of the VDR target genes, such as antimicrobial peptide cathelicidin, at the transcriptional level. Furthermore, the role of probiotics in regulating VDR signaling was tested in vivo using a Salmonella-colitis model in VDR knockout mice. Probiotic treatment conferred physiological and histologic protection from Salmonella-induced colitis in VDR+/+mice, whereas probiotics had no effects in the VDR−/−mice. Probiotic treatment also enhanced numbers of Paneth cells, which secrete AMPs for host defense. These data indicate that the VDR pathway is required for probiotic protection in colitis. Understanding how probiotics enhance VDR signaling and inhibit inflammation will allow probiotics to be used effectively, resulting in innovative approaches to the prevention and treatment of chronic inflammation.

scholarly journals Eriodictyol ameliorated cognitive dysfunction in APP/PS1 mice through inhibited ferroptosis via vitamin D receptor mediated Nrf2 activation

2021 ◽  
Author(s):  
Lin Li ◽  
Wenjun Li ◽  
Xiangru Zheng ◽  
Qinglong Liu ◽  
Qian Du ◽  
...  
Keyword(s):  
Vitamin D ◽  
Signaling Pathway ◽  
Western Blotting ◽  
Vitamin D Receptor ◽  
Amyloid Β ◽  
Qpcr Assay ◽  
Aβ Aggregation ◽  
The Brain

Abstract Background Alzheimer's disease (AD) is the most common type of neurodegenerative disease in contemporary era, and it is still clinically incurable. Eriodictyol, a natural flavonoid compound mainly exists in citrus fruits and some Chinese herbal medicine, has been reported with its effect of anti-inflammatory, antioxidant, anti-cancer and neuroprotective effects. However, there are few studies on the anti-AD effect and molecular mechanism of eriodictyol. Methods APP/PS1 mice were treated with eriodictyol and the cognitive function of mice was assessed by behavioral tests. The level of amyloid-β (Aβ) aggregation and hyper-phosphorylation of Tau in the brain of mice were detected by histological analysis and Western blotting. Meanwhile, HT-22 cells which induced by amyloid-β peptide (1-42) (Aβ1−42) oligomer were treated with eriodictyol after which cell viability was determined and the production of p-Tau was tested by Western blotting. Then, the characteristics of ferroptosis, including iron aggregation, lipid peroxidation and the expression of glutathione peroxidase type 4(GPX4), were determined both in vivo and in vitro by Fe straining, Western blotting and qPCR assay. Additionally, the expression level of Vitamin D receptor (VDR) and the activity of nuclear factor erythroid 2-related factor 2/heme oxygenase-1 (Nrf2/HO-1) signaling pathway were tested by Western blotting and qPCR assay. After that, the HT-22 cells with VDR knockout were used to explore the potential mechanisms and the relationship between VDR and Nrf2 was further assessed by coimmunoprecipitation assay and bioinformatics analysis. Results Eriodictyol obviously ameliorated cognitive deficits in APP/PS1 mice, suppressed Aβ aggregation and the phosphorylated level Tau in the brain of APP/PS1 mice. Meanwhile, eriodictyol could inhibit Tau hyper-phosphorylation and neurotoxicity in HT-22 cells induced by Aβ1−42 oligomer. Furthermore, both in vivo and in vitro, eriodictyol showed the anti-ferroptosis effect and its mechanism may connected with the activation of Nrf2/HO-1 signaling pathway. Additionally, the further experiment explains that the activation of Nrf2/HO-1 signaling pathway with eriodictyol treatment mediated by VDR. Conclusions Eriodictyol alleviated memory impairment and AD-like pathological changes via activating Nrf2/HO-1 signaling pathway mediated by VDR, which provide a new possibility for the treatment of AD.

scholarly journals Vitamin D Signaling in Gastro-Rheumatology: From Immuno-Modulation to Potential Clinical Applications

2021 ◽  
Vol 22 (5) ◽  
pp. 2456
Author(s):  
Cristiano Pagnini ◽  
Andrea Picchianti-Diamanti ◽  
Vincenzo Bruzzese ◽  
Roberto Lorenzetti ◽  
Michele Maria Luchetti ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Inflammatory Diseases ◽  
Treatment Protocols ◽  
In Vivo Models ◽  
Bowel Diseases ◽  
Vitamin D Supplements ◽  
Vitamin D Signaling

In the last decades, the comprehension of the pathophysiology of bone metabolism and its interconnections with multiple homeostatic processes has been consistently expanded. The branch of osteoimmunology specifically investigating the link between bone and immune system has been developed. Among molecular mediators potentially relevant in this field, vitamin D has been recently pointed out, and abnormalities of the vitamin D axis have been described in both in vitro and in vivo models of inflammatory bowel diseases (IBD) and arthritis. Furthermore, vitamin D deficiency has been reported in patients affected by IBD and chronic inflammatory arthritis, thus suggesting the intriguing possibility of impacting the disease activity by the administration vitamin D supplements. In the present review, the complex interwoven link between vitamin D signaling, gut barrier integrity, microbiota composition, and the immune system was examined. Potential clinical application exploiting vitamin D pathway in the context of IBD and arthritis is presented and critically discussed. A more detailed comprehension of the vitamin D effects and interactions at molecular level would allow one to achieve a novel therapeutic approach in gastro-rheumatologic inflammatory diseases through the design of specific trials and the optimization of treatment protocols.

scholarly journals The vitamin D receptor in cancer

2008 ◽  
Vol 67 (2) ◽  
pp. 115-127 ◽  
Author(s):  
James Thorne ◽  
Moray J. Campbell
Keyword(s):  
Vitamin D ◽  
Cell Fate ◽  
Vitamin D Receptor ◽  
De Novo ◽  
Lithocholic Acid ◽  
Cell Types ◽  
Cell Fate Decisions ◽  
Wide Range

Over the last 25 years roles have been established for vitamin D receptor (VDR) in influencing cell proliferation and differentiation. For example, murine knock-out approaches have revealed a role for the VDR in controlling mammary gland growth and function. These actions appear widespread, as the enzymes responsible for 1α,25-dihydroxycholecalciferol generation and degradation, and the VDR itself, are all functionally present in a wide range of epithelial and haematopoietic cell types. These findings, combined with epidemiological and functional data, support the concept that local, autocrine and paracrine VDR signalling exerts control over cell-fate decisions in multiple cell types. Furthermore, the recent identification of bile acid lithocholic acid as a VDR ligand underscores the environmental sensing role for the VDR.In vitroandin vivodissection of VDR signalling in cancers (e.g. breast, prostate and colon) supports a role for targeting the VDR in either chemoprevention or chemotherapy settings. As with other potential therapeutics, it has become clear that cancer cells displayde novoand acquired genetic and epigenetic mechanisms of resistance to these actions. Consequently, a range of experimental and clinical options are being developed to bring about more targeted actions, overcome resistance and enhance the efficacy of VDR-centred therapeutics.

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