scholarly journals Vitamin D: Nutrient, Hormone, and Immunomodulator

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1656 ◽  
Author(s):  
Francesca Sassi ◽  
Cristina Tamone ◽  
Patrizia D’Amelio
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Immune Cells ◽  
Critical Role ◽  
Active Form ◽  
Experimental Studies ◽  
Vitamin D Metabolism ◽  
Classical Action ◽  
Calcium Phosphorus ◽  
Specific Alteration

The classical functions of vitamin D are to regulate calcium-phosphorus homeostasis and control bone metabolism. However, vitamin D deficiency has been reported in several chronic conditions associated with increased inflammation and deregulation of the immune system, such as diabetes, asthma, and rheumatoid arthritis. These observations, together with experimental studies, suggest a critical role for vitamin D in the modulation of immune function. This leads to the hypothesis of a disease-specific alteration of vitamin D metabolism and reinforces the role of vitamin D in maintaining a healthy immune system. Two key observations validate this important non-classical action of vitamin D: first, vitamin D receptor (VDR) is expressed by the majority of immune cells, including B and T lymphocytes, monocytes, macrophages, and dendritic cells; second, there is an active vitamin D metabolism by immune cells that is able to locally convert 25(OH)D3 into 1,25(OH)2D3, its active form. Vitamin D and VDR signaling together have a suppressive role on autoimmunity and an anti-inflammatory effect, promoting dendritic cell and regulatory T-cell differentiation and reducing T helper Th 17 cell response and inflammatory cytokines secretion. This review summarizes experimental data and clinical observations on the potential immunomodulating properties of vitamin D.

scholarly journals Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

2016 ◽  
Vol 96 (1) ◽  
pp. 365-408 ◽  
Author(s):  
Sylvia Christakos ◽  
Puneet Dhawan ◽  
Annemieke Verstuyf ◽  
Lieve Verlinden ◽  
Geert Carmeliet
Keyword(s):  
Vitamin D ◽  
Cancer Progression ◽  
Dna Sequences ◽  
Critical Role ◽  
Active Form ◽  
Physiological Role ◽  
Vitamin D Metabolism ◽  
Technological Advances ◽  
Hydrogen Deuterium ◽  
Direct Binding

1,25-Dihydroxvitamin D3 [1,25(OH)2D3] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH)2D3 action involves the direct binding of the 1,25(OH)2D3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH)2D3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH)2D3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

scholarly journals Common and personal target genes of the micronutrient vitamin D in primary immune cells from human peripheral blood

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Andrea Hanel ◽  
Antonio Neme ◽  
Marjo Malinen ◽  
Emmi Hämäläinen ◽  
Henna-Riikka Malmberg ◽  
...  
Keyword(s):  
Vitamin D ◽  
Immune System ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Active Form ◽  
Biologically Active ◽  
Expression Change

AbstractVitamin D is essential for the function of the immune system. In this study, we treated peripheral blood mononuclear cells (PBMCs) of healthy adults with the biologically active form of vitamin D3, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) using two different approaches: single repeats with PBMCs obtained from a cohort of 12 individuals and personalized analysis based on triplicates of five study participants. This identified 877 (cohort approach) and 3951 (personalized approach) genes that significantly (p < 0.05) changed their expression 24 h after 1,25(OH)2D3 stimulation. From these, 333 and 1232 were classified as supertargets, a third of which were identified as novel. Individuals differed largely in their vitamin D response not only by the magnitude of expression change but also by their personal selection of (super)target genes. Functional analysis of the target genes suggested the overarching role of vitamin D in the regulation of metabolism, proliferation and differentiation, but in particular in the control of functions mediated by the innate and adaptive immune system, such as responses to infectious diseases and chronic inflammatory disorders. In conclusion, immune cells are an important target of vitamin D and common genes may serve as biomarkers for personal responses to the micronutrient.

scholarly journals Problems in differential diagnosis of secondary hyperparathyroidism

2021 ◽  
Vol 38 (1) ◽  
pp. 161-167
Author(s):  
S. G. Shulkina ◽  
D. O. Sirin ◽  
E. N. Smirnova ◽  
V. G. Zhelobov ◽  
N. Yu. Kolomeets ◽  
...  
Keyword(s):  
Vitamin D ◽  
Differential Diagnosis ◽  
Kidney Disease ◽  
Secondary Hyperparathyroidism ◽  
Vitamin D Deficiency ◽  
Clinical Case ◽  
Kidney Diseases ◽  
Active Form ◽  
Renal Tubules ◽  
Vitamin D Metabolism

Hyperparathyroidism is an endocrine disease characterized by excessive production of parathyroid hormone in the main cells of the parathyroid glands. Depending on the cause of this disease, there are primary, secondary (SHPT) and tertiary hyperparathyroidism. The most common causes of SHPT are vitamin D deficiency and chronic kidney disease (CKD). Vitamin D is converted to its active form by hydroxylation in the renal tubules. Developmental abnormalities and chronic kidney diseases lead to atrophy of the tubular epithelial cells that causes a violation of vitamin D metabolism and the development of SHPT, which in turn are accompanied by a violation of calcium-phosphorus metabolism and a syndrome of musculoskeletal disorders. This article presents an analysis of a clinical case of a patient diagnosed secondary hyperparathyroidism against the background of vitamin D deficiency combined with polycystic kidney disease. This clinical case reflects the complexity of the differential diagnosis of the disease and the tactics of patient's management.

scholarly journals Vitamin D, invariant natural killer T-cells and experimental autoimmune disease

2011 ◽  
Vol 71 (1) ◽  
pp. 62-66 ◽  
Author(s):  
Margherita T. Cantorna ◽  
Jun Zhao ◽  
Linlin Yang
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Immune System ◽  
Vitamin D Deficiency ◽  
Natural Killer ◽  
Active Form ◽  
Inkt Cells ◽  
Invariant Natural Killer ◽  
Experimental Autoimmune ◽  
Natural Killer T

Vitamin D is an important regulator of the immune system in general and multiple sclerosis in particular. Experimentally (i), invariant natural killer T (iNKT) cells have been shown to be important suppressors of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE; an animal model of multiple sclerosis). Conversely, in experimental allergic asthma iNKT cells are required for disease induction and are therefore pathogenic. The active form of vitamin D (calcitriol) suppresses EAE. The development of EAE symptoms is accelerated in vitamin D deficiency. Interestingly experimental asthma is less severe in vitamin D deficiency although there is no effect of calcitriol on disease severity. The data suggest that an important target of vitamin D in EAE and asthma are the iNKT cells. Vitamin D and/or vitamin D receptor deficiency results in the impaired development of iNKT cells. Vitamin D is critical very early during development of the immune system. Low levels of vitamin D in utero resulted in significantly reduced numbers of iNKT cells that failed to recover when calcitriol was used to supplement neonatal or adult mice. The data suggest that one of the consequences of early vitamin D deficiency is a reduction in the numbers of iNKT cells that develop. The iNKT cells are required for the beneficial effects of calcitriol in EAE. The important role of vitamin D on iNKT cells could impact the development of human immune-mediated diseases including multiple sclerosis and asthma.

Assessment of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D3 concentrations in male and female multiple sclerosis patients and control volunteers

2007 ◽  
Vol 13 (5) ◽  
pp. 670-672 ◽  
Author(s):  
M.S. Barnes ◽  
M.P. Bonham ◽  
P.J. Robson ◽  
J.J. Strain ◽  
A.S. Lowe-Strong ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Active Form ◽  
Plasma Concentrations ◽  
Secondary Analysis ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Multiple Sclerosis Patients ◽  
And Control

Populations with insufficient ultraviolet exposure and who consume diets low in vitamin D have low vitamin D status (plasma 25-hydroxyvitamin D (25(OH)D) concentrations) and a reported higher incidence of multiple sclerosis (MS). The active form of vitamin D, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), is an effective anti-inflammatory molecule. No research to date has assessed 1,25(OH)2D3 concentrations in individuals with MS. In this study, plasma concentrations of 25(OH)D, 1,25(OH)2D 3 and parathyroid hormone (PTH) were measured in 29 individuals with MS and 22 age- and sex-matched control volunteers. There were no significant differences in plasma PTH, 25(OH)D and 1,25(OH)2D3 concentrations between individuals with MS and control volunteers. Women with MS had significantly higher 25(OH)D and 1,25(OH)2D3 concentrations than men with MS (79.1 ±45.4 versus 50.2±15.3 nmol/L, P=0.019 and 103.8± 36.8 versus 70.4±28.7 pmol/L, P=0.019, respectively). There was a significant positive correlation between 25(OH)D and 1,25(OH)2D 3 concentrations in all subjects (r=0.564, P=0.000), but secondary analysis revealed that the correlation was driven by women with MS (r=0.677, P= 0.001). Significant sex differences in vitamin D metabolism were observed and were most marked in individuals with MS, suggesting that vitamin D requirements may differ between the sexes, as well as by underlying disease state. Multiple Sclerosis 2007; 13: 670-672. http://msj.sagepub.com

scholarly journals OR13-01 Comparison of Vitamin D Metabolism in Deficient and Sufficient States

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Artem Zhukov ◽  
Alexandra Povaliaeva ◽  
Ekaterina Pigarova ◽  
Larisa Dzeranova ◽  
Victor Bogdanov ◽  
...  
Keyword(s):  
Vitamin D ◽  
Biochemical Parameters ◽  
Oral Intake ◽  
Vitamin D Metabolites ◽  
Loading Dose ◽  
Healthy Individuals ◽  
Vitamin D Metabolism ◽  
Calcium Phosphorus ◽  
Group A ◽  
Group B

Abstract Objective: to study the differences in calcium-phosphorus and vitamin D metabolism in healthy individuals with deficient and sufficient baseline state of vitamin D. Materials and methods: The study included 16 young conditionally healthy individuals, divided into two equal groups: with levels of 25(OH)D below and above 30 ng/ml determined by the immunochemiluminescent method (Group A and Group B respectively; DEQAS certified). All participants were evaluated for the biochemical parameters of blood and urine, characterizing calcium-phosphorus metabolism, PTH by commercial methods, and vitamin D metabolites (25(OH)D3, 25(OH)D2, 3-epi-25(OH)D3 and 24,25(OH)2D3) by HPLC/MS-MS before oral intake of 150 000 IU of an aqueous solution of cholecalciferol and 7 days after administration. Results: At baseline, the level of vitamin D metabolite 25(OH)D2 in Group B was lower with no significant differences in other studied parameters. In group A, strong positive correlations were observed between levels 25(OH)D3 and 3-epi-25(OH)D3, 24,25(OH)2D3, while in group B there were no such associations. After taking a loading dose of cholecalciferol, the groups showed generally similar changes in the studied vitamin D metabolites: a statistically significant increase in 25(OH)D3, 3-epi-25(OH)D3, a decrease in 25(OH)D2, and a ratio of 24,25(OH)2D3 to 25(OH)D3. However, the level of 24,25(OH)2D3 did not change in group B, with a significant increase in group A. The medians of the studied biochemical parameters in blood/urine, as well as PTH, remained unchanged in both groups. Conclusion: In patients with inadequate baseline levels of 25(OH)D, after a loading dose of cholecalciferol, there is a tendency to formation of more inactive forms of vitamin D. These deviations in the metabolism of vitamin D need to be clarified, since they can potentially affect the effectiveness of cholecalciferol therapy.

Pathophysiology of chronic kidney disease-mineral and bone disorder

2015 ◽  
Author(s):  
Alexandra Voinescu ◽  
Nadia Wasi Iqbal ◽  
Kevin J. Martin
Keyword(s):  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Parathyroid Hormone ◽  
Kidney Disease ◽  
Fibroblast Growth Factor 23 ◽  
Serum Levels ◽  
Mineral And Bone Disorder ◽  
Vitamin D Metabolism ◽  
Bone Disorder ◽  
Calcium Phosphorus

Chronic kidney disease is associated with the inability to control normal mineral homeostasis, resulting in abnormalities in serum levels of calcium, phosphorus, parathyroid hormone, fibroblast growth factor 23 (FGF23) and vitamin D metabolism. These disturbances lead to the development of secondary hyperparathyroidism, skeletal abnormalities, vascular calcifications, and other systemic manifestations. Traditionally, mineral and bone abnormalities seen in chronic kidney disease were included in the term ‘renal osteodystrophy’. More recently, the term chronic kidney disease-mineral and bone disorder was introduced to define the biochemical abnormalities of phosphorus, parathyroid hormone, FGF23, calcium, or vitamin D metabolism, abnormalities in bone remodelling and mineralization, and vascular or other soft tissue calcifications.

scholarly journals A review of vitamin D and its importance to the health of dairy cattle

2020 ◽  
Vol 87 (S1) ◽  
pp. 84-87
Author(s):  
Jaka Jakob Hodnik ◽  
Jožica Ježek ◽  
Jože Starič
Keyword(s):  
Vitamin D ◽  
Dairy Cattle ◽  
Active Form ◽  
Dairy Farm ◽  
Sun Exposure ◽  
Short Review ◽  
The European Union ◽  
Vitamin D Metabolism ◽  
Milk Fever ◽  
Veterinary Faculty

AbstractThis Research Reflection short review will discuss vitamin D metabolism, its role in nutrition, disease prevention, and welfare of dairy cattle, as well as its toxicity. Vitamin D is an important fat-soluble vitamin. However, some researchers regard it as a hormone due to its function in the organism. Its role is not limited just to Ca homoeostasis and bone metabolism but is also associated with immunity. In dairy cattle it is known for preventing milk fever. Cows can acquire vitamin D in many ways for example through feed, parenteral injections or through UVB irradiation from the sun or artificial lighting. The vitamin D in feed can either be plant-/ fungi- based ergocalciferol or animal-based cholecalciferol. There is currently only one registered feed vitamin D supplement for cattle in the European Union and it is cholecalciferol. Animals can also synthesize their own vitamin D when 7-dihydrocholesterol in the skin is irradiated with UVB light resulting in cholecalciferol production. Despite its importance, many cattle are deficient in vitamin D due to inadequate supplementation or insufficient sun exposure. In a study performed at the Veterinary Faculty in Slovenia 12 high producing Holstein Friesian cows at a commercial dairy farm were blood tested for vitamin D status for three succeeding months and all but one were vitamin D insufficient in all testings. The cows were not exposed to direct sunlight and the content of vitamin D3 in feed was <400 IU/kg dry matter, which is less than half of the NRC (2001) recommendation. Deficiency can also occur due to diseases affecting the gastrointestinal tract, such as paratuberculosis, which lower the absorptive capacity of the gut. Vitamin D can be toxic if cows are over-supplemented or consume large quantities of plants like Trisetum flavescens, which contain an active form of vitamin D-calcitriol or its glycosides, that are activated by digestion in the rumen.

scholarly journals Immunologic Effects of Vitamin D on Human Health and Disease

Nutrients ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 2097 ◽  
Author(s):  
Nipith Charoenngam ◽  
Michael F. Holick
Keyword(s):  
Vitamin D ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Active Form ◽  
Experimental Studies ◽  
Vitamin D Supplementation ◽  
Peripheral Blood Mononuclear ◽  
Hydroxyvitamin D ◽  
Increased Risk ◽  
25 Hydroxyvitamin D

Vitamin D is responsible for regulation of calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. It is also known as an immunomodulatory hormone. Experimental studies have shown that 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts immunologic activities on multiple components of the innate and adaptive immune system as well as endothelial membrane stability. Association between low levels of serum 25-hydroxyvitamin D and increased risk of developing several immune-related diseases and disorders, including psoriasis, type 1 diabetes, multiple sclerosis, rheumatoid arthritis, tuberculosis, sepsis, respiratory infection, and COVID-19, has been observed. Accordingly, a number of clinical trials aiming to determine the efficacy of administration of vitamin D and its metabolites for treatment of these diseases have been conducted with variable outcomes. Interestingly, recent evidence suggests that some individuals might benefit from vitamin D more or less than others as high inter-individual difference in broad gene expression in human peripheral blood mononuclear cells in response to vitamin D supplementation has been observed. Although it is still debatable what level of serum 25-hydroxyvitamin D is optimal, it is advisable to increase vitamin D intake and have sensible sunlight exposure to maintain serum 25-hydroxyvitamin D at least 30 ng/mL (75 nmol/L), and preferably at 40–60 ng/mL (100–150 nmol/L) to achieve the optimal overall health benefits of vitamin D.

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