scholarly journals Crosstalk between Vitamin D Metabolism, VDR Signalling, and Innate Immunity

2016 ◽  
Vol 2016 ◽  
pp. 1-5 ◽  
Author(s):  
Rui Lin
Keyword(s):  
Vitamin D ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Active Form ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Vitamin D Metabolism ◽  
Dihydroxyvitamin D ◽  
Clinical Responses ◽  
Vitamin D Supplements

The primary function of vitamin D is to regulate calcium homeostasis, which is essential for bone formation and resorption. Although diet is a source of vitamin D, most foods are naturally lacking vitamin D. Vitamin D is also manufactured in the skin through a photolysis process, leading to a process called the “sunshine vitamin.” The active form of vitamin D, 1,25-dihydroxyvitamin D (calcitriol), is biosynthesised in the kidney through the hydroxylation of 25-hydroxycholecalciferol by the CYP27B1 enzyme. It has been found that several immune cells express the vitamin D receptor (VDR) and CYP27B1; of the latter, synthesis is determined by several immune-specific signals. The realisation that vitamin D employs several molecular mechanisms to regulate innate immune responses is more recent. Furthermore, evidence collected from intervention studies indicates that vitamin D supplements may boost clinical responses to infections. This review considers the current knowledge of how immune signals regulate vitamin D metabolism and how innate immune system function is modulated by ligand-bound VDR.

scholarly journals Canonical and Noncanonical Autophagy as Potential Targets for COVID-19

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1619 ◽  
Author(s):  
Melissa Bello-Perez ◽  
Isabel Sola ◽  
Beatriz Novoa ◽  
Daniel J. Klionsky ◽  
Alberto Falco
Keyword(s):  
Molecular Mechanisms ◽  
Viral Infections ◽  
Current Knowledge ◽  
Therapeutic Targets ◽  
Innate Immune ◽  
Interacting Proteins ◽  
Innate Immune Responses ◽  
Molecular Machinery ◽  
Autophagy Pathway

The SARS-CoV-2 pandemic necessitates a review of the molecular mechanisms underlying cellular infection by coronaviruses, in order to identify potential therapeutic targets against the associated new disease (COVID-19). Previous studies on its counterparts prove a complex and concomitant interaction between coronaviruses and autophagy. The precise manipulation of this pathway allows these viruses to exploit the autophagy molecular machinery while avoiding its protective apoptotic drift and cellular innate immune responses. In turn, the maneuverability margins of such hijacking appear to be so narrow that the modulation of the autophagy, regardless of whether using inducers or inhibitors (many of which are FDA-approved for the treatment of other diseases), is usually detrimental to viral replication, including SARS-CoV-2. Recent discoveries indicate that these interactions stretch into the still poorly explored noncanonical autophagy pathway, which might play a substantial role in coronavirus replication. Still, some potential therapeutic targets within this pathway, such as RAB9 and its interacting proteins, look promising considering current knowledge. Thus, the combinatory treatment of COVID-19 with drugs affecting both canonical and noncanonical autophagy pathways may be a turning point in the fight against this and other viral infections, which may also imply beneficial prospects of long-term protection.

scholarly journals Reshaping the way we view vitamin D signalling and the role of vitamin D in health

2004 ◽  
Vol 17 (2) ◽  
pp. 241-248 ◽  
Author(s):  
James C. Fleet ◽  
Jie Hong ◽  
Zhentao Zhang
Keyword(s):  
Vitamin D ◽  
Transcriptional Activation ◽  
Mode Of Action ◽  
Uv Light ◽  
Active Form ◽  
Vitamin D Metabolism ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D ◽  
Molecular Mode

AbstractAlthough the biological requirement for vitamin D can be met by epidermal exposure to UV light, there are a number of conditions where this production does not occur or is not sufficient to meet biological needs. When this happens, vitamin D must be consumed and is a nutrient. However, two distinct observations have caused researchers to rethink certain dogma in vitamin D biology. First, it appears that in addition to the hormonally active form of 1,25 dihydroxyvitamin D (1,25(OH)2D), circulating levels of 25 hydroxyvitamin D have a critical importance for optimal human health. This and other data suggest that extra-renal production of 1,25(OH)2D contributes to Ca homeostasis and cancer prevention. Second, in addition to its role in the transcriptional activation of genes through the vitamin D receptor there is now compelling evidence that 1,25(OH)2D has a second molecular mode of action; the rapid activation of second-messenger and kinase pathways. The purpose of this second mode of action is only now being explored. The present review will discuss how these two areas are reshaping our understanding of vitamin D metabolism and action.

scholarly journals Vitamin D, infections and immunity

2021 ◽  
Author(s):  
Aiten Ismailova ◽  
John H. White
Keyword(s):  
Vitamin D ◽  
Immune Responses ◽  
Current Knowledge ◽  
Intestinal Flora ◽  
Antibacterial Properties ◽  
Vitamin D Supplementation ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Skeletal Health ◽  
Vitamin D Signaling

AbstractVitamin D, best known for its role in skeletal health, has emerged as a key regulator of innate immune responses to microbial threat. In immune cells such as macrophages, expression of CYP27B1, the 25-hydroxyvitamin D 1α-hydroxylase, is induced by immune-specific inputs, leading to local production of hormonal 1,25-dihydroxyvitamin D (1,25D) at sites of infection, which in turn directly induces the expression of genes encoding antimicrobial peptides. Vitamin D signaling is active upstream and downstream of pattern recognition receptors, which promote front-line innate immune responses. Moreover, 1,25D stimulates autophagy, which has emerged as a mechanism critical for control of intracellular pathogens such as M. tuberculosis. Strong laboratory and epidemiological evidence links vitamin D deficiency to increased rates of conditions such as dental caries, as well as inflammatory bowel diseases arising from dysregulation of innate immune handling intestinal flora. 1,25D is also active in signaling cascades that promote antiviral innate immunity; 1,25D-induced expression of the antimicrobial peptide CAMP/LL37, originally characterized for its antibacterial properties, is a key component of antiviral responses. Poor vitamin D status is associated with greater susceptibility to viral infections, including those of the respiratory tract. Although the severity of the COVID-19 pandemic has been alleviated in some areas by the arrival of vaccines, it remains important to identify therapeutic interventions that reduce disease severity and mortality, and accelerate recovery. This review outlines of our current knowledge of the mechanisms of action of vitamin D signaling in the innate immune system. It also provides an assessment of the therapeutic potential of vitamin D supplementation in infectious diseases, including an up-to-date analysis of the putative benefits of vitamin D supplementation in the ongoing COVID-19 crisis.

scholarly journals Vitamin D and COVID-19: A Physiological Perspective

2021 ◽  
Vol 8 (5) ◽  
pp. 4358-4366
Author(s):  
Pendhamma Sindhusen
Keyword(s):  
Vitamin D ◽  
Active Form ◽  
Renin Angiotensin System ◽  
Vitamin D Supplementation ◽  
Respiratory Illnesses ◽  
Angiotensin Converting Enzyme 2 ◽  
Dihydroxyvitamin D ◽  
Microbial Infections ◽  
Vitamin D Supplements ◽  
Amount Of Knowledge

Already known to be capable of enhancing the performance of the immune system, preclude microbial infections, and reduce susceptibility to influenza, Vitamin D, or 1,25-dihydroxyvitamin D (1,25(OH)2D) as an active form, it has maintained a positive reputation in discourses regarding COVID-19 for a lengthy amount of time. Its deficiency is statistically correlated with infection of the disease, the severity thereof, and fatalities therefrom. There have also existed suggestions that Vitamin D supplements could either prevent contracting SARS-CoV-2, the Coronavirus that causes the disease, or alleviate the symptoms it is capable of begetting, since data has established a relationship between Vitamin D supplementation and the severity of respiratory illnesses and certain assays indicated optimistic results in COVID-19 patients supplemented with the vitamin. Accordingly, a great deal of research and efforts have been put into investigating the physiological mechanisms in the human body attributable to the vitamin's reputation against the Coronavirus and combined with what was already discovered before the advent of SARS-CoV-2, a great amount of knowledge has consequently been unveiled. Via regulation of various pathways, 1,25(OH)2D promotes the production of antimicrobial peptides, autophagy, the integrity and impermeability of cellular junctions against pathogens, as well as mitigate the consequences of SARS-CoV-2 infection such as cytokine storm through immunomodulation of the T cell differentiation pathways and lung injury through stimulation of the Angiotensin-Converting Enzyme 2 (ACE2) and manipulation of the Renin-Angiotensin System (RAS). Nevertheless, the unfortunate fact is that Vitamin D deficiency still plagues the global population across all age categories, which could have translated into humanity's heightened exposure to the Coronavirus. With the COVID-19 pandemic inexorably raging on with no prospect of termination observable in the foreseeable future, this review article provides a concise yet thorough insight into that vast knowledge, which could illuminate the significance of Vitamin D amidst the current predicament experienced by mankind, as well as instigate more curiosity as to any current unclarity related to the issue and ignite further discussions and studies that would deliver more understanding to the vitamin's role as a safeguard against SARS-CoV-2

scholarly journals Lower placental 25-hydroxyvitamin D3 (25(OH)D3) and higher placental CYP27B1 and 25(OH)D3 ratio in preterm birth

2020 ◽  
Vol 9 ◽  
Author(s):  
Rima Irwinda ◽  
Biancha Andardi
Keyword(s):  
Vitamin D ◽  
Preterm Birth ◽  
Active Form ◽  
Cross Sectional Study ◽  
Nutritional Deficiencies ◽  
Vitamin D Metabolism ◽  
Cross Sectional ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
25 Hydroxyvitamin D

Abstract Neonatal mortality rates in Indonesia are still at an alarming rate, with preterm birth as one of the causes. Nutritional deficiencies such as low level of vitamin D is suspected to be the risk factors of preterm birth but still a little knowledge about it. Vitamin D metabolism includes 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), as the inactive and active form, with the help of 1α-hydroxylase (CYP27B1) enzyme. Our study aims to determine the differences of 25(OH)D3, 1,25(OH)2D3 and CYP27B1 enzyme in term and preterm birth. A cross-sectional study was performed in Cipto Mangunkusumo National General Hospital, Jakarta, Indonesia, in January–June 2017. The blood sample was taken soon after delivery, to examine maternal 25(OH)D3 and 1,25(OH)2D3 in serum and tissue placenta, as well as placental CYP27B1 enzyme. Statistical analysis using SPPS version 20 was used to find significances. There were a total of sixty subjects in this study, with term-preterm birth group ratio 1:1. We found that placental 25(OH)D3 was significantly low (P = 0⋅001), and CYP27B1/25(OH)D3 ratio was high in preterm birth. Also, there were significant negative correlations found in CYP27B1 level and both placental 25(OH)D3 (r 0⋅481, P < 0⋅001) and 1,25(OH)2D3 (r −0⋅365, P = 0⋅004) levels. Our study concludes that preterm birth showed lower placental 25(OH)D3 status, and higher CYP27B1/25(OH)D3 ratio compared to term pregnancy.

scholarly journals MicroRNAs from Snellenius manilae bracovirus regulate innate and cellular immune responses of its host Spodoptera litura

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Cheng-Kang Tang ◽  
Chih-Hsuan Tsai ◽  
Carol-P. Wu ◽  
Yu-Hsien Lin ◽  
Sung-Chan Wei ◽  
...  
Keyword(s):  
Immune Responses ◽  
Spodoptera Litura ◽  
Molecular Mechanisms ◽  
Innate Immune ◽  
Sequencing Analysis ◽  
Innate Immune Responses ◽  
Cellular Immune Responses ◽  
Next Generation Sequencing Analysis ◽  
Cellular Immune ◽  
Generation Sequencing

AbstractTo avoid inducing immune and physiological responses in insect hosts, parasitoid wasps have developed several mechanisms to inhibit them during parasitism, including the production of venom, specialized wasp cells, and symbioses with polydnaviruses (PDVs). These mechanisms alter the host physiology to give the wasp offspring a greater chance of survival. However, the molecular mechanisms for most of these alterations remain unclear. In the present study, we applied next-generation sequencing analysis and identified several miRNAs that were encoded in the genome of Snellenius manilae bracovirus (SmBV), and expressed in the host larvae, Spodoptera litura, during parasitism. Among these miRNAs, SmBV-miR-199b-5p and SmBV-miR-2989 were found to target domeless and toll-7 in the host, which are involved in the host innate immune responses. Microinjecting the inhibitors of these two miRNAs into parasitized S. litura larvae not only severely decreased the pupation rate of Snellenius manilae, but also restored the phagocytosis and encapsulation activity of the hemocytes. The results demonstrate that these two SmBV-encoded miRNAs play an important role in suppressing the immune responses of parasitized hosts. Overall, our study uncovers the functions of two SmBV-encoded miRNAs in regulating the host innate immune responses upon wasp parasitism.

Mechanisms implicated in the growth regulatory effects of vitamin D in breast cancer.

2002 ◽  
pp. 45-59 ◽  
Author(s):  
K W Colston ◽  
C M√∏rk Hansen
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Bone Mineralization ◽  
Active Form ◽  
Cell Types ◽  
Cell Cycle Regulators ◽  
Dihydroxyvitamin D ◽  
Cell Growth And Differentiation ◽  
Regulatory Effects ◽  
Apoptotic Effects

It is now well established that, in addition to its central role in the maintenance of extracellular calcium levels and bone mineralization, 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)), the active form of vitamin D, also acts as a modulator of cell growth and differentiation in a number of cell types, including breast cancer cells. The anti-proliferative effects of 1,25(OH)(2)D(3) have been linked to suppression of growth stimulatory signals and potentiation of growth inhibitory signals, which lead to changes in cell cycle regulators such as p21(WAF-1/CIP1) and p27(kip1), cyclins and retinoblastoma protein as well as induction of apoptosis. Such studies have led to interest in the potential use of 1,25(OH)(2)D(3) in the treatment or prevention of certain cancers. Since this approach is limited by the tendency of 1,25(OH)(2)D(3) to cause hypercalcaemia, synthetic vitamin D analogues have been developed which display separation of the growth regulating effects from calcium mobilizing actions. This review examines mechanisms by which 1,25(OH)(2)D(3) and its active analogues exert both anti-proliferative and pro-apoptotic effects and describes some of the synthetic analogues that have been shown to be of particular interest in relation to breast cancer.

scholarly journals Vitamin D-Mediated Hypercalcemia: Mechanisms, Diagnosis, and Treatment

2016 ◽  
Vol 37 (5) ◽  
pp. 521-547 ◽  
Author(s):  
Peter J. Tebben ◽  
Ravinder J. Singh ◽  
Rajiv Kumar
Keyword(s):  
Vitamin D ◽  
Vitamin D Receptor ◽  
Active Form ◽  
Elevated Serum ◽  
Diagnosis And Treatment ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Stone Formers ◽  
25 Hydroxyvitamin D

AbstractHypercalcemia occurs in up to 4% of the population in association with malignancy, primary hyperparathyroidism, ingestion of excessive calcium and/or vitamin D, ectopic production of 1,25-dihydroxyvitamin D [1,25(OH)2D], and impaired degradation of 1,25(OH)2D. The ingestion of excessive amounts of vitamin D3 (or vitamin D2) results in hypercalcemia and hypercalciuria due to the formation of supraphysiological amounts of 25-hydroxyvitamin D [25(OH)D] that bind to the vitamin D receptor, albeit with lower affinity than the active form of the vitamin, 1,25(OH)2D, and the formation of 5,6-trans 25(OH)D, which binds to the vitamin D receptor more tightly than 25(OH)D. In patients with granulomatous disease such as sarcoidosis or tuberculosis and tumors such as lymphomas, hypercalcemia occurs as a result of the activity of ectopic 25(OH)D-1-hydroxylase (CYP27B1) expressed in macrophages or tumor cells and the formation of excessive amounts of 1,25(OH)2D. Recent work has identified a novel cause of non-PTH-mediated hypercalcemia that occurs when the degradation of 1,25(OH)2D is impaired as a result of mutations of the 1,25(OH)2D-24-hydroxylase cytochrome P450 (CYP24A1). Patients with biallelic and, in some instances, monoallelic mutations of the CYP24A1 gene have elevated serum calcium concentrations associated with elevated serum 1,25(OH)2D, suppressed PTH concentrations, hypercalciuria, nephrocalcinosis, nephrolithiasis, and on occasion, reduced bone density. Of interest, first-time calcium renal stone formers have elevated 1,25(OH)2D and evidence of impaired 24-hydroxylase-mediated 1,25(OH)2D degradation. We will describe the biochemical processes associated with the synthesis and degradation of various vitamin D metabolites, the clinical features of the vitamin D-mediated hypercalcemia, their biochemical diagnosis, and treatment.

Vitamin D

2005 ◽  
Vol 289 (1) ◽  
pp. F8-F28 ◽  
Author(s):  
Adriana S. Dusso ◽  
Alex J. Brown ◽  
Eduardo Slatopolsky
Keyword(s):  
Vitamin D ◽  
Target Genes ◽  
Endocrine System ◽  
Target Cells ◽  
Vitamin D Metabolism ◽  
Diverse Range ◽  
Hydroxyvitamin D ◽  
Dihydroxyvitamin D ◽  
Single Receptor ◽  
Recent Developments

The vitamin D endocrine system plays an essential role in calcium homeostasis and bone metabolism, but research during the past two decades has revealed a diverse range of biological actions that include induction of cell differentiation, inhibition of cell growth, immunomodulation, and control of other hormonal systems. Vitamin D itself is a prohormone that is metabolically converted to the active metabolite, 1,25-dihydroxyvitamin D [1,25(OH)2D]. This vitamin D hormone activates its cellular receptor (vitamin D receptor or VDR), which alters the transcription rates of target genes responsible for the biological responses. This review focuses on several recent developments that extend our understanding of the complexities of vitamin D metabolism and actions: the final step in the activation of vitamin D, conversion of 25-hydroxyvitamin D to 1,25(OH)2D in renal proximal tubules, is now known to involve facilitated uptake and intracellular delivery of the precursor to 1α-hydroxylase. Emerging evidence using mice lacking the VDR and/or 1α-hydroxylase indicates both 1,25(OH)2D3-dependent and -independent actions of the VDR as well as VDR-dependent and -independent actions of 1,25(OH)2D3. Thus the vitamin D system may involve more than a single receptor and ligand. The presence of 1α-hydroxylase in many target cells indicates autocrine/paracrine functions for 1,25(OH)2D3in the control of cell proliferation and differentiation. This local production of 1,25(OH)2D3is dependent on circulating precursor levels, providing a potential explanation for the association of vitamin D deficiency with various cancers and autoimmune diseases.

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.

Sign in / Sign up

Export Citation Format

Share Document