1, 25-Dihydroxycholecalciferol in the Pathogenesis of the Hypercalcæmia of Sarcoidosis

Papapoulos, Socrates E.; Fraher, L. J.; Sandler, L. M.; Clemens, Thomas L.; Lewin, I. G.; O’Riordan, J. L. H.

doi:10.1016/s0140-6736(79)91076-6

Cited by 217 publications

(97 citation statements)

References 12 publications

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“…Patients with overproduction of calcitriol due to uncontrolled extrarenal CYP1a expression, e.g., sarcoidosis patients [31][32][33][34], suffer from peripheral immunological anergy and show enhanced numbers of Treg cells [35]. In vitro, calcitriol-stimulated dendritic cells can promote the development of Treg cells [10] and calcitriol directly enhances expression of IL-10 by Th cells [11].…”

Section: Discussionmentioning

confidence: 99%

1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells

et al. 2008

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Section: Discussionmentioning

confidence: 99%

1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells

et al. 2008

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“…The original description of extra-renal 1 -OHase expression was based on studies of the granulomatous disease sarcoidosis, which frequently presents with associated hypercalcaemia (Papapoulos et al 1979, Barbour et al 1981. Enzyme-activity analyses using lymph-node homogenates and pulmonary alveolar macrophages from patients with sarcoidosis showed high levels of 1 -OHase activity (Adams et al 1983, Adams & Gacad 1985, Reichel et al 1987.…”

Section: Extra-renal Expression Of 1 -Ohasementioning

confidence: 99%

1alpha-Hydroxylase and the action of vitamin D

Hewison¹,

Zehnder²,

Bland³

et al. 2000

Journal of Molecular Endocrinology

201

125

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The active form of vitamin D, 1,25-dihydroxvitamin D 3 (1,25(OH) 2 D 3 ), is a pleiotropic hormone whose actions include the regulation of calcium homeostasis, control of bone cell differentiation and modification of immune responses. Synthesis of 1,25(OH) 2 D 3 from the major circulating metabolite, 25-hydroxyvitamin D 3 (25(OH)D 3 ), is catalysed by a mitochondrial cytochrome P450 enzyme, 25-hydroxyvitamin D-1 -hydroxylase (1 -OHase). Although 1 -OHase is expressed predominantly in the kidney, extra-renal production of 1,25(OH) 2 D 3 has also been demonstrated in tissues such as lymph nodes and skin. The tight regulation of 1 -OHase which occurs in both renal and peripheral tissues has made studies of the expression and regulation of this enzyme remarkably difficult. However, the recent cloning of mouse, rat and human cDNAs for 1 -OHase (CYP1 /Cyp1 ) has enabled a more thorough characterization of this enzyme. In particular, analysis of the CYP1 gene has identified mutations causing the inherited disorder vitamin D-dependent rickets type 1, also known as pseudo-vitamin D deficiency rickets. Studies from our own group have focused on the distribution of 1 -OHase in both renal and extra-renal tissues. Data indicate that the enzyme is expressed throughout the nephron, suggesting discrete endocrine and paracrine/autocrine functions. Further immunohistochemical analyses have shown that the enzyme is widely distributed in extra-renal tissues, and this appears to be due to the same gene product as the kidney. Collectively, these observations have raised important new questions concerning the role of 1 -OHase in vitamin D signalling at a local level. The relationship between expression of protein for 1 -OHase and enzyme activity has yet to be fully characterized and may be dependent on membrane proteins such as megalin. Similarly, elucidation of the mechanisms involved in differential regulation of renal and extra-renal 1,25(OH) 2 D 3 production will be essential to our understanding of the tissue-specific functions of 1 -OHase. These and other issues are discussed in the current review.

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“…Recently, the monocytes/macrophages isolated from sarcoidosis granuloma or from the alveolar levage fluid were shown to have 1α hydroxylase activity capable of synthesizing 1,25(OH) 2 D3 from 25-OH D3. 11 Subsequently, this was shown in other granulomatous diseases and cancers also. 12 Human peripheral blood mononuclear cells also synthesize 1,25(OH) 2 D3 in response to immune stimuli, such as IFN-γ or bacterial antigens agonists of TLRs, such as lipopolysaccharides.…”

Section: Vitamin D3 and Monocyte/macrophagesmentioning

confidence: 88%

Role of Active Vitamin D3 in Immunity

Singh¹,

Verma²,

Singh³

et al. 2017

Indian Journal of Medical Biochemistry

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precursor 25 hydroxy cholecalciferol. Only recently, its crucial role as a potential immune modulator has been recognized. Clear identification of its well-documented roles in immune response and autoimmunity has led it to being actively pursued as a potential therapeutic agent. 1,2 Vitamin D3 influences all the key cells of the immune system and produces intracrine and paracrine effects on them. Most immune cells have the enzyme system to produce the active form of vitamin D3. It is an inhibitor of differentiation and maturation of dendritic cells (DCs) and decreases their antigen-presenting activity. It acts directly on T cells and alters the profile of their proliferation and differentiation. It promotes anti-inflammatory environment by inhibiting the Th1 and Th17 cells and promoting the Th 2 and T reg cell differentiations. Vitamin D3 induces antimicrobial effects in monocytes/macrophages by enhancing their phagocyte activity as well as helping the synthesis of antimicrobial peptides. Sunlight-mediated epidermal expression of 1,25(OH) 2 D3 acts as the link between the environment and immune system. It induces suppression of cutaneous immune response through the T-regulatory cells. Overall, it is considered an important regulator of both innate and adaptive immune systems. There is an emerging view that the vitamin D deficiency, which is widely prevalent these days, could have an important role in immune disorders, especially the autoimmune diseases. 2In this review, we present an overview of the current knowledge on vitamin D as an immunomodulator with the underlying molecular mechanisms and its possible role in immunological response with future implications. VITAMIN D-THE MOLECULEErgocalciferol, vitamin D2, and cholecalciferol, vitamin D3, are the two major forms of vitamin D. Vitamin D2 is synthesized by plants and fungi, while vitamin D3 is produced in large quantities in humans by photosynthesis in the skin. The ultraviolet (UV) light falling on the skin catalyzes the conversion of 7-dehydro-cholesterol into the previtamin D, which then spontaneously ABSTRACT Introduction:The active vitamin D3-1,25 dihydroxy cholecalciferol-is the key player in calcium and phosphorus metabolism and skeletal growth and functions. However, recent new developments have revealed its role in other tissues as well, referred to as the nonclassical actions of vitamin D. Not only the endocrinal effects, evidence indicates that vitamin D3 also has autocrine and paracrine functions due to its extrarenal synthesis by many cells, including the immune cells. All cells of the immune system have vitamin D receptors and show wide-ranging effects to it. It impacts both the innate and adaptive immune systems and the overall influence points to anti-infective, anti-inflammatory, immunosuppressive, and regulatory roles. It shows a significant role in chronic inflammatory and autoimmune diseases as well in susceptibility to infections.In this review, newer developments on the role of vitamin D in immunity and the underlying mechanism are d...

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1, 25-Dihydroxycholecalciferol in the Pathogenesis of the Hypercalcæmia of Sarcoidosis

Cited by 217 publications

References 12 publications

1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells

1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells

1alpha-Hydroxylase and the action of vitamin D

Role of Active Vitamin D3 in Immunity

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1, 25-Dihydroxycholecalciferol in the Pathogenesis of the Hypercalcæmia of Sarcoidosis

Cited by 217 publications

References 12 publications

1,25‐dihydroxyvitamin D3 promotes IL‐10 production in human B cells

1,25‐dihydroxyvitamin D3 promotes IL‐10 production in human B cells

1alpha-Hydroxylase and the action of vitamin D

Role of Active Vitamin D3 in Immunity

Contact Info

Product

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1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells

1,25‐dihydroxyvitamin D₃ promotes IL‐10 production in human B cells