scholarly journals Vitamin D signaling in a mouse allergic sensitization model

2020 ◽  
Vol 90 (5-6) ◽  
pp. 385-388
Author(s):  
Renata Lucas ◽  
Johanna Mihály ◽  
Janine Gericke ◽  
Dániel Törőcsik ◽  
Ralph Rühl

Abstract. Vitamin D mediated signalling in the skin is discussed controversially for its beneficial or detrimental influence. In this study we examined various factors involved in Vitamin D-mediated signalling in a mouse model for allergic dermatitis with systemic (OVA IP) and systemic plus topical allergic sensitization (OVA IP + EC). We found that the major enzyme responsible for 1,25-Vitamin D3 synthesis, the 1-hydoxylase CYP27B1 (3,6-fold for OVA IP and 2,7-fold for OVA IP + EC), the vitamin D receptor (not altered) and the sensitive Vitamin D-mediated signalling target gene CYP24A1 (65-fold in OVA IP and 726-fold in OVA IP + EC) are upregulated after systemic and systemic plus topical allergic sensitization (OVA IP + EC). In consequence, active Vitamin D-mediated signalling is involved in systemic as well as systemic/topical allergic sensitization in mouse skin.

2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
Eleanor Yusupov ◽  
Melissa Li-Ng ◽  
Simcha Pollack ◽  
James K. Yeh ◽  
Mageda Mikhail ◽  
...  

Background. The role of vitamin D in the body's ability to fight influenza and URI's may be dependent on regulation of specific cytokines that participate in the host inflammatory response. The aim of this study was to test the hypothesis that vitamin D can influence intracellular signaling to regulate the production of cytokines.Subjects and Methods. This study was a 3-month prospective placebo-controlled trial of vitamin D3 supplementation in ambulatory adults [Li-Ng et al., 2009]. 162 volunteers were randomized to receive either 50 μg/d(2000 IU) of vitamin D3 or matching placebo. 25(OH)D and the levels of 10 different cytokines (IL-2, 4, 5, 6, 8, 10, 13, GM-CSF, IFN-γ, TNF-α) were measured in the serum of participants at baseline and the final visit. There were 6 drop-outs from the active vitamin D group and 8 from the placebo group.Results. In the active vitamin D group, we found a significant median percent decline in levels of GM-CSF (−62.9%,P<.0001), IFN-γ(−38.9%,P<.0001), IL-4 (−50.8%,P=.001), IL-8 (−48.4%,P<.0001), and IL-10 (−70.4%,P<.0001). In the placebo group, there were significant declines for GM-CSF (−53.2%,P=.0007) and IFN-γ(−34.4%,P=.0011). For each cytokine, there was no significant difference in the rate of decline between the two groups. 25(OH)D levels increased in the active vitamin D group from a mean of64.3±25.4 nmol/L to88.5±23.2 nmol/L.Conclusions. The present study did not show that vitamin D3 supplementation changed circulating cytokine levels among healthy adults.


2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Nakhoul Nakhoul ◽  
Tina Thawko ◽  
Evgeny Farber ◽  
Inbal Dahan ◽  
Hagar Tadmor ◽  
...  

Background. Diabetic nephropathy (DN) is one of the most common microvascular complications of diabetes and is the leading cause of end-stage renal disease (ESRD) and replacement therapy worldwide. Vitamin D levels in DN patients are very low due to the decrease in the synthesis and activity of 1-α hydroxylase in the proximal tubule cells and decrease in the vitamin D receptor abundance. To date, few studies have shown the antioxidant effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] on hyperglycemia-induced renal injury. The selective activator of the vitamin D receptor, paricalcitol, reduces proteinuria and slows the progression of kidney injury. The precise mechanism through which vitamin D affects diabetic status and provides kidney protection remains to be determined. Methods. Diabetes mellitus (DM) was induced in 94 8-week-old DBA/2J mice by intraperitoneal injection of streptozotocin (STZ). DM mice were randomly divided into receiving vehicle or treatment with paricalcitol, the active vitamin D analog, 1 week after DM induction or paricalcitol treatment 3 weeks after DM induction. An additional control group of healthy wild-type mice was not treated. Urine albumin, blood urea nitrogen, and creatinine levels were measured before and at the end of the paricalcitol treatment. Periodic acid-Schiff, immunohistochemistry staining, and western blot of the renal tissues of vitamin D receptor, villin, nephrin, and podocin expressions, were analyzed. Results. Paricalcitol treatment restored villin, nephrin, and podocin protein levels that were downregulated upon DM induction, and reduced fibronectin protein level. Vitamin D receptor activation by paricalcitol may reduce proteinuria of DN in mice and alleviate high-glucose-induced injury of kidney podocytes by regulating the key molecules such nephrin-podocin. Conclusions. Paricalcitol treatment was associated with improved structural changes in type 1 diabetic mice including upregulation of vitamin D receptor expression, and decreased fibrosis markers such as fibronectin. These effects may contribute to the consistent benefit of vitamin D analog to slow the deterioration in glomerular function and reduce the risk of ESRD in patients with type 1 and 2 diabetes mellitus. Our results suggest that additional use of paricalcitol may be beneficial in treating patients with diabetes under standard therapeutic strategies.


Endocrinology ◽  
2016 ◽  
Vol 158 (3) ◽  
pp. 503-515 ◽  
Author(s):  
Duncan M. Gascoyne ◽  
Linden Lyne ◽  
Hayley Spearman ◽  
Francesca M. Buffa ◽  
Elizabeth J. Soilleux ◽  
...  

Abstract Plasmablastic B-cell malignancies include plasmablastic lymphoma and subsets of multiple myeloma and diffuse large B-cell lymphomaDLBCL. These diseases can be difficult to diagnose and treat, and they lack well-characterized cell line models. Here, immunophenotyping and FOXP1 expression profiling identified plasmablastic characteristics in DLBCL cell lines HLY-1 and SU-DHL-9, associated with CTNNAL1, HPGD, RORA, IGF1, and/or vitamin D receptor (VDR) transcription. We demonstrated VDR protein expression in primary plasmablastic tumor cells and confirmed in cell lines expression of both VDR and the metabolic enzyme CYP27B1, which catalyzes active vitamin D3 production. Although Vdr and Cyp27b1 transcription in normal B cells were activated by interleukin 4 (IL-4) and CD40 signaling, respectively, unstimulated malignant plasmablastic cells lacking IL-4 expressed both VDR and CYP27B1. Positive autoregulation evidenced intact VDR function in all plasmablastic lines, and inhibition of growth by active vitamin D3 was both dependent on MYC protein inhibition and could be enhanced by cotreatment with a synthetic ROR ligand SR-1078. Furthermore, a VDR polymorphism, FOK1, was associated with greater vitamin D3–dependent growth inhibition. In summary, HLY-1 provides an important model of strongly plasmablastic lymphoma, and disruption of VDR pathway activity may be of therapeutic benefit in both plasmablastic lymphoma and myeloma.


2021 ◽  
pp. 1-14
Author(s):  
Elham Kazemian ◽  
Sayed Hossein Davoodi ◽  
Mohammad Esmaeil Akbari ◽  
Nariman Moradi ◽  
Safoora Gharibzadeh ◽  
...  

Author(s):  
Nakhoul Farid ◽  
Nakhoul Rola ◽  
Elias A. T. Koch ◽  
Nakhoul Nakhoul

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