THE 20-EPI MODIFICATION IN THE VITAMIN D SERIES: SELECTIVE ENHANCEMENT OF "NON-CLASSICAL" RECEPTOR-MEDIATED EFFECTS

Seasonal variations in UV-B radiation may influence vitamin D status, and this, in turn, may influence the risk of bronchiolitis hospitalization. The aim of this study was using a causal inference approach to investigate, simultaneously, the interrelationships between personal and environmental risk factors at birth/hospital admission (RFBH), serum vitamin D levels and bronchiolitis hospitalization. A total of 63 children (<2 years old) hospitalized for bronchiolitis (34 RSV-positive) and 63 controls were consecutively enrolled (2014–2016). Vitamin D levels and some RFBH (birth season, birth weight, gestational age, gender, age, weight, hospitalization season) were recorded. The discovered RFBH effects on the risk ok bronchiolitis hospitalization were decomposed into direct and vitamin-D mediated ones through Mediation Analysis. Winter-spring season (vs. summer-autumn) was significantly associated with lower vitamin D levels (mean difference −11.14 nmol/L). Increasing serum vitamin D levels were significantly associated with a lower risk of bronchiolitis hospitalization (OR = 0.84 for a 10-nmol/L increase). Winter-spring season and gestational age (one-week increase) were significantly and directly associated with bronchiolitis hospitalization (OR = 6.37 and OR = 0.78 respectively), while vitamin D-mediated effects were negligible (1.21 and 1.02 respectively). Using a comprehensive causal approach may enhance the understanding of the complex interrelationships among RFBH, vitamin D and bronchiolitis hospitalization.

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Vitamin D metabolism, sex hormones, and male reproductive function

Reproduction ◽

10.1530/rep-12-0064 ◽

2012 ◽

Vol 144 (2) ◽

pp. 135-152 ◽

Cited By ~ 35

Author(s):

Martin Blomberg Jensen

Keyword(s):

Vitamin D ◽

Association Studies ◽

Reproductive Function ◽

Hormone Production ◽

Vitamin D Metabolism ◽

Mediated Effects ◽

Male Reproductive Function ◽

Expression Studies ◽

Metabolizing Enzyme ◽

And Function

The spectrum of vitamin D (VD)-mediated effects has expanded in recent years, and VD is now recognized as a versatile signaling molecule rather than being solely a regulator of bone health and calcium homeostasis. One of the recently identified target areas of VD is male reproductive function. The VD receptor (VDR) and the VD metabolizing enzyme expression studies documented the presence of this system in the testes, mature spermatozoa, and ejaculatory tract, suggesting that both systemic and local VD metabolism may influence male reproductive function. However, it is still debated which cell is the main VD target in the testis and to what extent VD is important for sex hormone production and function of spermatozoa. This review summarizes descriptive studies on testicular VD metabolism and spatial distribution of VDR and the VD metabolizing enzymes in the mammalian testes and discusses mechanistic and association studies conducted in animals and humans. The reviewed evidence suggests some effects of VD on estrogen and testosterone biosynthesis and implicates involvement of both systemic and local VD metabolism in the regulation of male fertility potential.

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A Lipid-Based Nanocarrier Containing Active Vitamin D3 Ameliorates NASH in Mice via Direct and Intestine-Mediated Effects on Liver Inflammation

Biological and Pharmaceutical Bulletin ◽

10.1248/bpb.b20-00432 ◽

2020 ◽

Vol 43 (9) ◽

pp. 1413-1420 ◽

Cited By ~ 1

Author(s):

Yunmei Mu ◽

Jinting Li ◽

Jeong-Hun Kang ◽

Hinako Eto ◽

Khadijah Zai ◽

...

Keyword(s):

Vitamin D ◽

Liver Inflammation ◽

Active Vitamin ◽

Active Vitamin D ◽

Mediated Effects

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Role of vitamin D in cell-cell interaction of fetal endothelial progenitor cells and umbilical cord endothelial cells in a preeclampsia-like model

AJP Cell Physiology ◽

10.1152/ajpcell.00109.2019 ◽

2019 ◽

Vol 317 (2) ◽

pp. C348-C357 ◽

Cited By ~ 2

Author(s):

L. Brodowski ◽

B. Schröder-Heurich ◽

C. A. Hubel ◽

T. H. Vu ◽

C. S. von Kaisenberg ◽

...

Keyword(s):

Vitamin D ◽

Endothelial Cells ◽

Endothelial Cell ◽

Endothelial Dysfunction ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Progenitor ◽

Cord Serum ◽

Mediated Effects ◽

Fetal Serum

Maternal endothelial dysfunction is a cental feature of preeclampsia (PE), a hypertensive disorder of pregnancy. Factors in the maternal circulation are thought to contribute to this endothelial dysfunction. Although understudied, factors in the fetal circulation may influence fetal endothelial cell interactions with endothelial progenitor cells as critical steps in placental angiogenesis. We hypothesize that cell-cell interactions that are important for pregnancy health are impaired by fetal serum from PE pregnancies and that 1,25(OH)2-vitamin D3 attenuates the negative effects of this serum on cell function. We tested the ability of fetal cord blood-derived endothelial progenitor cells [endothelial colony-forming cells (ECFCs)] to invade into established monolayers and capillary tubule-like structures of human fetal umbilical venous endothelial cells (HUVECs), while in the presence/absence of fetal cord serum from uncomplicated or PE pregnancies, and tested the ability of 1,25(OH)2-vitamin D3 to modulate the serum-mediated effects. PE cord serum reduced the invasion of fetal ECFCs into HUVEC monolayers or tubule networks. Vitamin D attenuated these effects of PE fetal serum on endothelial functional properties. Immunocytochemical studies revealed involvement of VE-cadherin contacts in interactions between ECFCs and mature fetal endothelial cells. PE cord serum reduces the ability of fetal endothelial progenitor cells to incorporate into fetal endothelial cell networks. Physiologic concentrations of vitamin D reverse these PE serum-mediated effects. These data appear consistent with lines of evidence that vitamin D has antipreeclampsia effects.

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MicroRNA-mediated effects of vitamin D on leptin-stimulated tumour growth

Nature Reviews Endocrinology ◽

10.1038/nrendo.2014.179 ◽

2014 ◽

Vol 10 (12) ◽

pp. 702-702

Keyword(s):

Vitamin D ◽

Tumour Growth ◽

Mediated Effects

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IL-33/Vitamin D Crosstalk in Psoriasis-Associated Osteoporosis

Frontiers in Immunology ◽

10.3389/fimmu.2020.604055 ◽

2021 ◽

Vol 11 ◽

Author(s):

Massimo De Martinis ◽

Lia Ginaldi ◽

Maria Maddalena Sirufo ◽

Enrica Maria Bassino ◽

Francesca De Pietro ◽

...

Keyword(s):

Vitamin D ◽

Skin Barrier ◽

Th2 Cells ◽

Functional Link ◽

Mediated Effects ◽

Metabolic Functions ◽

Immune Mediated ◽

Increased Risk ◽

Pleiotropic Action

Patients with psoriasis (Pso) and, in particular, psoriatic arthritis (PsoA) have an increased risk of developing osteoporosis (OP). It has been shown that OP is among the more common pathologies associated with Pso, mainly due to the well-known osteopenizing conditions coexisting in these patients. Pso and OP share common risk factors, such as vitamin D deficiency and chronic inflammation. Interestingly, the interleukin (IL)-33/ST2 axis, together with vitamin D, is closely related to both Pso and OP. Vitamin D and the IL-33/ST2 signaling pathways are closely involved in bone remodeling, as well as in skin barrier pathophysiology. The production of anti-osteoclastogenic cytokines, e.g., IL-4 and IL-10, is promoted by IL-33 and vitamin D, which are stimulators of both regulatory and Th2 cells. IL-33, together with other Th2 cytokines, shifts osteoclast precursor differentiation towards macrophage and dendritic cells and inhibits receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclastogenesis by regulating the expression of anti-osteoclastic genes. However, while the vitamin D protective functions in OP and Pso have been definitively ascertained, the overall effect of IL-33 on bone and skin homeostasis, because of its pleiotropic action, is still controversial. Emerging evidence suggests a functional link between vitamin D and the IL-33/ST2 axis, which acts through hormonal influences and immune-mediated effects, as well as cellular and metabolic functions. Based on the actions of vitamin D and IL-33 in Pso and OP, here, we hypothesize the role of their crosstalk in the pathogenesis of both these pathologies.

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The role of vitamin D in autoimmune diseases: could sex make the difference?

Biology of Sex Differences ◽

10.1186/s13293-021-00358-3 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Maria Luisa Dupuis ◽

Maria Teresa Pagano ◽

Marina Pierdominici ◽

Elena Ortona

Keyword(s):

Vitamin D ◽

Autoimmune Diseases ◽

Vitamin D Receptor ◽

Immune Modulation ◽

Current Knowledge ◽

Active Form ◽

Adaptive Immune System ◽

Sex And Gender ◽

Mediated Effects

AbstractOver the last decades, a central role for vitamin D in immune modulation has been well established. The active form of vitamin D, i.e., 1,25-dihydroxyvitamin D, through the interaction with vitamin D receptor, exerts different activities on the innate and adaptive immune system, among which suppression of inflammation and promotion of tolerogenic responses. Vitamin D insufficiency has been linked to autoimmune disorders that commonly display significant differences between females and males due to genetic, epigenetic, hormonal, and environmental factors. Notably, a number of studies recently showed a cross-talk between vitamin D and the sex hormone estrogen. Estrogen-mediated effects on immune response may favor a Th1 profile or a Th2 profile, depending on hormone concentration. Thus, estrogen-mediated effects appear to be variable on autoimmunity depending on its concentration but also on the pathogenic mechanisms underlying the different autoimmune diseases (i.e., Th1- or Th2-mediated diseases). Notably, estrogen has been demonstrated to enhance vitamin D function favoring its accumulation, and increasing the expression of vitamin D receptor, thus resulting in a more potent anti-inflammatory response in females than males. On the other hand, vitamin D has been shown to downregulate in immune cells the expression of aromatase, which converts testosterone to estrogen, leading to a decrease in estrogen level. Overall, available data allow us to hypothesize a higher protective effect of vitamin D-based therapeutic approaches in women, at least in fertile age, than in men. Future studies are needed to expand current knowledge on the immunomodulatory role of vitamin D in a sex and gender perspective, paving the way to a more personalized therapeutic approach in autoimmune diseases.

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