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Hormones as Immune Modulating Agents
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
The precursor of VD3, cholecalciferol, is taken up in diet or synthesized in the skin under the influence of ultraviolet (UV) radiation. 25-Hydroxyvitamin D3 is generated in the liver and is further processed by 1-hydroxylase in the kidney. This latter enzyme is also present in monocytes/macrophages, keratinocytes, bone marrow, placenta, glial cells, and pneumocytes. The vitamin D receptor (VDR) is of 50 kDa molecular weight and is a member of the superfamily of steroid/thyroid hormone receptors. It interacts with vitamin D-responsive elements (VDRE) on DNA and also with the retinoic X receptor. Both positive (stimulation) and negative (inhibition) signaling is possible through VDRE. Vitamin D regulates the DNA binding subunit of NFkB. Protein kinase C is involved in receptor-mediated signaling by VD3. Within the immune system, monocytes/macrophages, activated T lymphocytes, B lymphocytes, and bone marrow cells express VDR [287,288].
Current Recommendations for the Treatment of Psoriasis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Topical vitamin D analogs used in psoriasis treatment include calcitriol, calcipotriene, and tacalcitol. These analogs all act by binding to the vitamin D receptor, which then binds to a region of DNA called the vitamin D response element. Its downstream effects result in inhibition of keratinocyte proliferation and stimulation of keratinocyte differentiation.8–10 Calcitriol has also been shown to be immunomodulatory by inhibiting T-cell activity and decreasing the production of TNF-alpha, interferon-gamma, IL-4, IL-6, and IL-12, all of which are implicated in psoriasis.11–13 Although vitamin D analogs alone have been shown to be less effective than high-potency corticosteroids, their use in combination with corticosteroids has an additive effect.14–16 The addition of vitamin D analogs may also reduce the frequency of corticosteroid use, thereby decreasing the risk of skin atrophy.17 The combination of calcipotriol and betamethasone dipropionate ointment was approved by the FDA for plaque psoriasis in 2004. A foam formulation of the drug was approved by the FDA in 2015, and was shown in clinical trials to have significantly greater efficacy than the ointment formulation.18
Protective effects of vitamin D3 (cholecalciferol) on vancomycin-induced oxidative nephrotoxic damage in rats
Published in Pharmaceutical Biology, 2023
Rouba Yasser Al-Sroji, Shaza Al-Laham, Ahmad Almandili
The majority of vitamin D3 in the body is obtained through sunlight-initiated biosynthesis in the skin. When the skin is exposed to UVB radiation and thermal stimulation, a7-dehydrocholesterol is converted to pre-vitamin D3 and then to vitamin D3 (Zella and DeLuca 2003). First, vitamin D3 is converted to 25(OH)D in the liver by hydroxylation; then the second hydroxylation occurs in the kidneys, which produces 1,25(OH)2D3, which is the biologically active form of vitamin D3. It binds to the nuclear vitamin D receptor (VDR) or the plasma membrane VDR. The biological actions of 1,25 (OH)2D3 mediate control gene expression (Deluca and Cantorna 2001; Zella and DeLuca 2003). VitD3-VDR forms homodimers or heterodimers with the retinoid X receptor (RXR), then the homodimers or heterodimers bind to vitamin D3 response elements (VDRE). Thus, the expression of specific target genes is activated (Dulak et al. 2000). The VDR mediates both genomic and non-genomic actions of vitamin D3. These two kinds of actions are involved in physiological processes through regulating the transcriptional activity of target genes and activation of intracellular second messengers, respectively (Feghali and Wright 1997; Donato et al. 2009).
Overview of gene expression techniques with an emphasis on vitamin D related studies
Published in Current Medical Research and Opinion, 2023
Jeffrey Justin Margret, Sushil K. Jain
The genomic effects of vitamin D are mediated by the vitamin D receptor (VDR); nearly 3% of the human genome is regulated by the active form of vitamin D62. VDR binds the active form of vitamin D to form a heterodimeric complex with the retinoic acid X receptor, which in turn binds to vitamin D response elements (VDRE) in the DNA. A variety of transcription factors attach to this complex, which results in either upregulation or downregulation of the genes involved in cell proliferation, differentiation, and mineral homeostasis63. The expression of vitamin D regulatory genes can be used as biomarkers for different actions of vitamin D in various tissues and the cells they express and for the assessment of susceptibilities64. It is important to study the distribution of VDR expression in different tissues to determine the function of vitamin D in regulating various biological processes. In addition, to determine the importance of local vitamin D synthesis, independent of synthesis taking place in the liver and kidney, it is vital to understand the expression of genes necessary for active vitamin D synthesis65.
Vitamin D deficiency is a risk factor for delayed tooth eruption associated with persistent primary tooth
Published in Acta Odontologica Scandinavica, 2021
Thaís Aparecida Xavier, Isabela Ribeiro Madalena, Raquel Assed Bezerra da Silva, Léa Assed Bezerra da Silva, Marcelo José Barbosa Silva, Andiara De Rossi, Erika Calvano Küchler, Sandra Yasuyo Fukada
In dental research, genetic polymorphisms in VDR have already been associated with some clinical conditions, such as periodontal disease [16] and dental caries in permanent and primary teeth [7,8]. VDR is a nuclear receptor that mediates the cellular effects of 1,25-dihydroxy vitamin D3 by binding to vitamin D response elements of target genes, resulting in gene transcription changes. Many of these target genes are crucial for tooth development and play an essential role in the different processes of tooth eruption and root resorption. A previous study in a Brazilian population demonstrated that apical root resorption of permanent teeth was associated with a genetic polymorphism in VDR [15]. Here, we show that the genetic polymorphisms rs2228570 and rs739837 in VDR are not associated with PPT or DTE.