Prolongation of the Survival of Murine Cardiac Allografts by the Vitamin D3 Analogue 1,25-Dihydroxy-Δ16-Cholecalciferol

Lemire, Jacques; Archer, Debra; Khulkarni, Anil; Ince, A.; Uskoković, Milan R.; Stepkowski, S.

doi:10.1097/00007890-199210000-00046

Cited by 57 publications

(25 citation statements)

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“…In animal models, vitamin D has been shown to prolong survival of liver, renal and cardiac allografts. 11,34,[38][39][40][41] Topical treatment with vitamin D has been shown to decrease the allo-stimulatory capacity of DCs in the skindraining lymph nodes, and enhanced the suppressive capacity of regulatory T cells. 42 The growing in vitro and animal literature demonstrating the effects of vitamin D on DC and T-cell populations support the hypothesis that vitamin D has a role in modulating GVHD.…”

Section: Discussionmentioning

confidence: 99%

“…In animal models, vitamin D has been shown to reduce airway inflammation in a rat asthma model, 6 and suppress or prevent autoimmune encephalomyelitis, 7 arthritis, 8 inflammatory bowel disease 9,10 and diabetes. 11 In addition, it has been shown that patients with systemic lupus erythematosus, Behcets Disease, Type 1 diabetes mellitus, and multiple sclerosis have low levels of vitamin D. [12][13][14][15][16][17] The impact of vitamin D on host immunity is mediated, in part, by its effect on DCs. In one study, vitamin D was shown to exert an immunomodulatory effect on myeloid DCs, suppressing Th1 responses.…”

Section: Introductionmentioning

confidence: 99%

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Low levels of 25-hydroxyvitamin D before allogeneic hematopoietic SCT correlate with the development of chronic GVHD

Glotzbecker

Aldridge

et al. 2012

Bone Marrow Transplant

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Vitamin D, a hormone involved in bone and calcium homeostasis, has been shown to have potent immunomodulatory effects. We performed a retrospective cohort analysis to evaluate whether monohydroxyvitamin D levels before allogeneic hematopoietic SCT (HSCT) correlate with the risk of GVHD. Fifty-three patients who underwent myeloablative HSCT were studied. Vitamin D levels were measured in serum samples obtained before HSCT. The median 25-hydroxyvitamin vitamin D level was 21.9 ng/mL (7.8-45.7). The cumulative incidence (CI) of grades II-IV acute GVHD at 100 days was 53.1% in patients with vitamin Do25, versus 33.3% in patients with vitamin DX25 ng/mL (P ¼ 0.13). The CI of chronic GVHD (cGVHD) at 2 years in patients with vitamin Do25 was 63.8%, compared with 23.8% in patients with vitamin DX25 ng/mL (P ¼ 0.009). Similarly, the 2 year CI of extensive cGVHD was significantly greater in patients with vitamin Do25 compared with those with vitamin DX25 ng/mL (54.5% versus 14.3%, P ¼ 0.005). In a multivariable competing risk model, low pre-transplant vitamin D levels remained a significant factor associated with cGVHD (hazard ratio ¼ 5.26, P ¼ 0.02). Our results demonstrate that vitamin D deficiency before HSCT is associated with an increased risk of cGVHD. (2013) 48, 593-597; doi:10.1038/bmt.2012 published online 24 September 2012 Keywords: Vitamin D; GVHD; hematopoietic SCT INTRODUCTION GVHD remains a significant cause of morbidity and mortality following allogeneic HSCT. Despite standard immune-suppression with a calcineurin inhibitor and MTX, grade II-IV acute GVHD rates range from 20-50% and chronic GVHD from 40-50% after BMT. Bone Marrow Transplantation

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Low levels of 25-hydroxyvitamin D before allogeneic hematopoietic SCT correlate with the development of chronic GVHD

Glotzbecker

Aldridge

et al. 2012

Bone Marrow Transplant

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“…1,25(OH) 2 D 3 and its analogues can prevent systemic lupus erythematosus in lpr/lpr mice (15), experimental allergic encephalomyelitis (16 -18), and autoimmune diabetes in nonobese diabetic mice (19). In addition, 1,25(OH) 2 D 3 and its analogues prolong the survival of heart (20,21) and small bowel allografts (22) and have been reported to inhibit, in association with cyclosporin A (CsA), not only acute but also chronic allograft rejection (23).…”

Section: Endritic Cells (Dc)mentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 Inhibits Differentiation, Maturation, Activation, and Survival of Dendritic Cells Leading to Impaired Alloreactive T Cell Activation

Penna

Adorini

2000

The Journal of Immunology

1,174

877

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1α,25-Dihydroxyvitamin D3 (1,25(OH)2D3), the active form of vitamin D3, is a potent immunomodulatory agent. Here we show that dendritic cells (DCs) are major targets of 1,25(OH)2D3-induced immunosuppressive activity. 1,25(OH)2D3 prevents the differentiation in immature DCs of human monocytes cultured with GM-CSF and IL-4. Addition of 1,25(OH)2D3 during LPS-induced maturation maintains the immature DC phenotype characterized by high mannose receptor and low CD83 expression and markedly inhibits up-regulation of the costimulatory molecules CD40, CD80, and CD86 and of class II MHC molecules. This is associated with a reduced capacity of DCs to activate alloreactive T cells, as determined by decreased proliferation and IFN-γ secretion in mixed leukocyte cultures. 1,25(OH)2D3 also affects maturing DCs, leading to inhibition of IL-12p75 and enhanced IL-10 secretion upon activation by CD40 ligation. In addition, 1,25(OH)2D3 promotes the spontaneous apoptosis of mature DCs. The modulation of phenotype and function of DCs matured in the presence of 1,25(OH)2D3 induces cocultured alloreactive CD4+ cells to secrete less IFN-γ upon restimulation, up-regulate CD152, and down-regulate CD154 molecules. The inhibition of DC differentiation and maturation as well as modulation of their activation and survival leading to T cell hyporesponsiveness may explain the immunosuppressive activity of 1,25(OH)2D3.

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“…In experimental studies, VDRA treatment improves survival of heart grafts (49,62) as well as survival of kidney (94), liver (95), and pancreatic islet grafts (38). Furthermore, its effects are additive to those of cyclosporine/tacrolimus (14,22,94), corticosteroids (58), mycophenolate (38, 126), and interferon-␤ (42).…”

Section: Role Of Vdra In Transplantationmentioning

confidence: 99%

A new role for vitamin D receptor activation in chronic kidney disease

Valdivielso

Cannata-Andía

Coll

et al. 2009

American Journal of Physiology-Renal Physiology

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Valdivielso JM, Cannata-Andía J, Coll B, Fernández E. A new role for vitamin D receptor activation in chronic kidney disease. Am J Physiol Renal Physiol 297: F1502-F1509, 2009. First published July 22, 2009 doi:10.1152/ajprenal.00130.2009.-Vitamin D has proven to be much more than a simple "calcium hormone." The fact that the vitamin D receptor has been found in cells not related to mineral metabolism supports that statement. The interest of nephrologists in vitamin D and its effects beyond mineral metabolism has increased over the last few years, evidencing the importance of this so-called "sunshine hormone." In the present review, we highlight the most recent developments in the traditional use of vitamin D in chronic kidney disease (CKD) patients, namely, the control of secondary hyperparathyroidism (sHPT). Furthermore, we also explore the data available regarding the new possible therapeutic uses of vitamin D for the treatment of other complications present in CKD patients, such as vascular calcification, left ventricular hypertrophy, or proteinuria. Finally, some still scarce but very promising data regarding a possible role of vitamin D in kidney transplant patients also are reviewed. The available data point to a potential beneficial effect of vitamin D in CKD patients beyond the control of mineral metabolism.VITAMIN D IS A STEROID HORMONE that has long been known for its important role in regulating body levels of calcium (Ca) and phosphorus (P) and in mineralization of bone. However, there is an increasing amount of data proving that vitamin D exerts its effects beyond kidney, intestine, and bone (Fig. 1). The active form of vitamin D (calcitriol) mediates its biological effects by binding to the vitamin D receptor (VDR), which then translocates to the nuclei of target cells (for review, see Ref. 47). The VDR is a ligand-activated transcription factor that, after activation, recruits cofactor molecules and binds to specific DNA binding sites to modify the expression of target genes. Ligand-mediated conformational changes of the VDR contribute to specific mechanisms in its signaling cascade. Thus the structural chemical modification of active vitamin D is a powerful tool in discovering new compounds that show selective activation of the VDR. Over the last years, a number of new VDR activators (VDRAs), defined as compounds that can bind to VDR and induce its activation, have been synthesized and used in several diseases, including in patients with CKD. Their potential as new therapeutic agents has boosted this area of research. Moreover, new evidence suggests that VDR polymorphisms may influence the response to VDRAs (125). Present Use of VDRAs in Patients with CKDOne of the main complications in patients with CKD is the development of secondary hyperparathyroidism (sHPT). In the past, the increase in parathyroid gland (PTG) size and parathyroid hormone (PTH) synthesis were attributed to a decrease in circulating Ca. As a result, patients with sHPT were treated with oral vitamin D metabolites to correct ...

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Prolongation of the Survival of Murine Cardiac Allografts by the Vitamin D3 Analogue 1,25-Dihydroxy-Δ16-Cholecalciferol

Cited by 57 publications

References 0 publications

Low levels of 25-hydroxyvitamin D before allogeneic hematopoietic SCT correlate with the development of chronic GVHD

Low levels of 25-hydroxyvitamin D before allogeneic hematopoietic SCT correlate with the development of chronic GVHD

1α,25-Dihydroxyvitamin D3 Inhibits Differentiation, Maturation, Activation, and Survival of Dendritic Cells Leading to Impaired Alloreactive T Cell Activation

A new role for vitamin D receptor activation in chronic kidney disease

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