scholarly journals Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility toCitrobacter rodentiumby suppressing mucosal Th17 responses

2012 ◽  
Vol 303 (12) ◽  
pp. G1299-G1311 ◽  
Author(s):  
Natasha R. Ryz ◽  
Scott J. Patterson ◽  
Yiqun Zhang ◽  
Caixia Ma ◽  
Tina Huang ◽  
...  

Vitamin D deficiency affects more that 1 billion people worldwide and is associated with an increased risk of developing a number of inflammatory/autoimmune diseases, including inflammatory bowel disease (IBD). At present, the basis for the impact of vitamin D on IBD and mucosal immune responses is unclear; however, IBD is known to reflect exaggerated immune responses to luminal bacteria, and vitamin D has been shown to play a role in regulating bacteria-host interactions. Therefore, to test the effect of active vitamin D on host responses to enteric bacteria, we gave 1,25(OH)2D3to mice infected with the bacterial pathogen Citrobacter rodentium, an extracellular microbe that causes acute colitis characterized by a strong Th1/Th17 immune response. 1,25(OH)2D3treatment of infected mice led to increased pathogen burdens and exaggerated tissue pathology. In association with their increased susceptibility, 1,25(OH)2D3-treated mice showed substantially reduced numbers of Th17 T cells within their infected colons, whereas only modest differences were noted in Th1 and Treg numbers. In accordance with the impaired Th17 responses, 1,25(OH)2D3-treated mice showed defects in their production of the antimicrobial peptide REG3γ. Taken together, these studies show that 1,25(OH)2D3suppresses Th17 T-cell responses in vivo and impairs mucosal host defense against an enteric bacterial pathogen.

Author(s):  
Amal Ahmed Mohamed ◽  
Eman Mohamed Salah Ahmed ◽  
Rasha T.A. Abdel-Aziz ◽  
Halaa H. Eldeeb Abdallah ◽  
Hadeel El-Hanafi ◽  
...  

2020 ◽  
Author(s):  
Siva Swapna Kasarla ◽  
Sujatha Dodoala ◽  
Sunitha Sampathi ◽  
Narendra Kumar Talluri

AbstractVitamin D deficiency is an endemic problem existing worldwide. Although several strategies were established to enhance vitamin D3 levels, studies specifically focussing inhibition of vitamin D metabolism which may prolong the availability of active vitamin D in pathological conditions are less explored. Studies also suggest that higher doses of vitamin D3 fail to achieve optimum vitamin D levels. In this context, we focussed on the enzyme CYP3A4 which promotes inactivation of active vitamin D. The current study was aimed to decipher the impact of chrysin, a proven CYP3A4 inhibitor as an intervention and its effects in combination with low dose vitamin D3 (40 IU) and bone health in vitamin D deficiency condition. The in-vivo activity of chrysin was evaluated on female Wistar albino rats fed with a vitamin D deficient diet to attain vitamin D deficiency for 28 days. Chrysin was given alone and in combination with calcium carbonate (CaCO3) and/or vitamin D3. All the therapeutic interventions were assessed for serum 25-OH-D3 by LC-MS, biochemical, urinary, and bone parameters. Animals treated with chrysin alone and in combination with low dose vitamin D3 and/or CaCO3 showed an eminent rise in serum 25-OH-D3 levels along with increased serum biochemical parameters. On contrary, a significant decrease in the urinary parameters followed by beneficial effects on bone parameters was noticed in contrast with the vitamin D deficient diet group. Our findings revealed that although chrysin alone showed a notable effect on 25-OH-D3 and osseous tissue, comparatively it showed intensified therapeutic effect in combination with vitamin D3 and CaCO3 which can be employed as a cost-effective option to improve bone health.Graphical Abstract


2019 ◽  
Vol 41 (3) ◽  
pp. 336-344
Author(s):  
Sérgio Gardano Elias Bucharles ◽  
Fellype Carvalho Barreto ◽  
Miguel Carlos Riella

Abstract Introduction: Treating secondary hyperparathyroidism (SHPT), a common condition associated with death in patients with chronic kidney disease, is a challenge for nephrologists. Calcimimetics have allowed the introduction of drug therapies no longer based on phosphate binders and active vitamin D. This study aimed to assess the safety and effectiveness of cinacalcet in managing chronic dialysis patients with severe SHPT. Methods: This retrospective study included 26 patients [age: 52 ± 12 years; 55% females; time on dialysis: 54 (4-236) months] on hemodialysis (N = 18) or peritoneal dialysis (N = 8) with severe SHPT (intact parathyroid hormone (iPTH) level > 600 pg/mL) and hyperphosphatemia and/or persistent hypercalcemia treated with cinacalcet. The patients were followed for 12 months. Their serum calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and iPTH levels were measured at baseline and on days 30, 60, 90, 180, and 365. Results: Patients with hyperphosphatemia (57.7%), hypercalcemia (23%), or both (19.3%) with iPTH > 600 pg/mL were prescribed cinacalcet. At the end of the study, decreases were observed in iPTH (1348 ± 422 vs. 440 ± 210 pg/mL; p < 0.001), Ca (9.5 ± 1.0 vs. 9.1 ± 0.6 mg/dl; p = 0.004), P (6.0 ± 1.3 vs. 4.9 ± 1.1 mg/dl; p < 0.001), and ALP (202 ± 135 vs. 155 ± 109 IU/L; p = 0.006) levels. Adverse events included hypocalcemia (26%) and digestive problems (23%). At the end of the study, 73% of the patients were on active vitamin D and cinacalcet. Three (11.5%) patients on peritoneal dialysis did not respond to therapy with cinacalcet, and their iPTH levels were never below 800 pg/mL. Conclusion: Cinacalcet combined with traditional therapy proved safe and effective and helped manage the mineral metabolism of patients with severe SHPT.


2008 ◽  
Vol 158 (4) ◽  
pp. 571-576 ◽  
Author(s):  
Lars Rejnmark ◽  
Peter Vestergaard ◽  
Lene Heickendorff ◽  
Leif Mosekilde

ObjectiveAlthough calcitriol (1,25(OH)2D) is considered the biologically active vitamin D metabolite, several studies have shown that calcidiol (25OHD) is the vitamin D metabolite that is most closely linked to parathyroid function and indices of calcium homeostasis. Moreover, low levels of 25OHD have been associated with increased risk of different diseases including cancer, diabetes, and myopathy.DesignCross-sectional study.MethodsWe studied relations between plasma concentrations of 25OHD, 1,25(OH)2D, and parathyroid hormone (PTH) in fasting plasma samples from 315 healthy postmenopausal women randomly selected from the local background population.ResultsP-1,25(OH)2D levels varied in a concentration-dependent manner with P-25OHD levels (P<0.001). Thus, P-1,25(OH)2D levels were the lowest in women with vitamin D insufficiency, i.e., P-1,25(OH)2D levels were reduced by approximately one-third in subjects with P-25OHD levels below 25 nmol/l compared with levels above 80 nmol/l (P<0.01). The association was most pronounced at P-25OHD concentrations below 80 nmol/l, whereas no major increase in P-1,25(OH)2D was observed at P-25OHD concentrations above 80 nmol/l. In multiple regression analysis, PTH was a minor although significant predictor of P-1,25(OH)2D levels.ConclusionsIn normal postmenopausal women, the conversion of 25OHD to active vitamin D depends on the substrate concentration. Our data support that vitamin D insufficiency should be considered at P-25OHD levels below 80 nmol/l.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2559
Author(s):  
María Dolores Arenas Jimenez ◽  
Emilio González-Parra ◽  
Marta Riera ◽  
Abraham Rincón Bello ◽  
Ana López-Herradón ◽  
...  

Background. In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. Methods. A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. Results. The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6–27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97–1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. Conclusions. Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.


2015 ◽  
Vol 2015 ◽  
pp. 1-14 ◽  
Author(s):  
Pei Li ◽  
Ting Wu ◽  
Xin Su ◽  
Yi Shi

Aspergillus fumigatus(A. fumigatus) is one of the most common fungi to cause diseases in humans. Recent evidence has demonstrated that airway epithelial cells play an important role in combatingA. fumigatusthrough inflammatory responses. Human airway epithelial cells have been proven to synthesize the active vitamin D, which plays a key role in regulating inflammation. The present study was conducted to investigate the impact ofA. fumigatusinfection on the activation of vitamin D and the role of vitamin D activation inA. fumigatus-elicited antifungal immunity in normal human airway epithelial cells. We found thatA. fumigatusswollen conidia (SC) induced the expression of 1α-hydroxylase, the enzyme catalyzing the synthesis of active vitamin D, and vitamin D receptor (VDR) in 16HBE cells and led to increased local generation of active vitamin D. Locally activated vitamin D amplified SC-induced expression of antimicrobial peptides in 16HBE cells but attenuated SC-induced production of cytokines in an autocrine fashion. Furthermore, we identifiedβ-glucan, the majorA. fumigatuscell wall component, as the causative agent for upregulation of 1α-hydroxylase and VDR in 16HBE cells. Therefore, activation of vitamin D is inducible and provides a bidirectional regulation of the responses toA. fumigatusin 16HBE cells.


2019 ◽  
Vol 220 (3) ◽  
pp. 514-523 ◽  
Author(s):  
Juan I Moliva ◽  
Michael A Duncan ◽  
Angélica Olmo-Fontánez ◽  
Anwari Akhter ◽  
Eusondia Arnett ◽  
...  

AbstractAs we age, there is an increased risk for the development of tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) infection. Few studies consider that age-associated changes in the alveolar lining fluid (ALF) may increase susceptibility by altering soluble mediators of innate immunity. We assessed the impact of adult or elderly human ALF during Mtb infection in vitro and in vivo. We identified amplification of pro-oxidative and proinflammatory pathways in elderly ALF and decreased binding capability of surfactant-associated surfactant protein A (SP-A) and surfactant protein D (SP-D) to Mtb. Human macrophages infected with elderly ALF–exposed Mtb had reduced control and fewer phagosome–lysosome fusion events, which was reversed when elderly ALF was replenished with functional SP-A/SP-D. In vivo, exposure to elderly ALF exacerbated Mtb infection in young mice. Our studies demonstrate how the pulmonary environment changes as we age and suggest that Mtb may benefit from declining host defenses in the lung mucosa of the elderly.


Sign in / Sign up

Export Citation Format

Share Document