Vitamin D3 down-regulates intracellular Toll-like receptor 9 expression and Toll-like receptor 9-induced IL-6 production in human monocytes

Dickie, Laura; Church, Leigh D; Coulthard, Lydia R.; Mathews, Rebeccah J.; Emery, Paul; McDermott, Michael F.

doi:10.1093/rheumatology/keq124

Cited by 157 publications

(104 citation statements)

References 11 publications

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“…Several pathways and cell types that are relevant to cardiovascular physiology and pathology are influenced by vitamin D metabolites as summarized in Figure 3 and the 53 There is some evidence that epigenetic mechanisms may be involved in the attenuation of Toll-like receptor-mediated inflammation by 1,25(OH) 2 D; the suppressor of cytokine signaling 1 is stimulated by 1,25(OH) 2 D via downregulation of proinflammatory microRNA-155 production in macrophages ( Figure 5). 49 In patients with type 2 diabetes mellitus, endoplasmic reticulum stress and the uptake of cholesterol by macrophages is suppressed by 1,25(OH) 2 intriguing information to suggest that polymorphisms in vitamin D metabolism genes may have a role in the early phases of islet autoimmunity.…”

Section: Mechanistic Basis Of the Effect Of 125(oh) 2 D On Cardiovasmentioning

confidence: 99%

Vitamin D and Cardiovascular Disease

Norman¹,

Powell

2014

Circulation Research

442

353

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Vitamin D (nutritional term for compounds with biological activity of 1α,25-dihydroxyvitamin D; also used to indicate summation of Vitamin D 2 and D 3 ) is a fat-soluble vitamin that functions as a steroid hormone. It plays a crucial role in mineral homeostasis and skeletal health and its deficiency classically leads to rickets in children and osteomalacia in adults. 1 Its primary action on the skeletal system is to regulate calcium and phosphorus metabolism by influencing intestinal absorption, bone resorption, and renal retention (Figure 1). Vitamin D metabolites also play an integral physiological role in nonskeletal tissues and have been implicated in a wide range of chronic pathology, including skin and autoimmune disease, cancer, diabetes mellitus, hypertension, and cardiovascular disease (CVD).2 Interest in the role of vitamin D in CVD arose from evidence of adverse cardiovascular effects of vitamin D deficiency in animal models, 3 and epidemiological studies reporting the increase in cardiovascular events in winter and at increasing distance from the equator. Various extrarenal tissues, including many cell types involved in CVD, also express CYP27B1 and are therefore able to produce 1,25(OH) 2 D. This local production and breakdown is not subject to the same feedback controls as renal production. Vitamin D Deficiency and ExcessThere is controversy about the definition of vitamin D deficiency (or hypovitaminosis D), the optimum serum level of 25(OH)D, and the dietary requirements of vitamin D.

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Section: Mechanistic Basis Of the Effect Of 125(oh) 2 D On Cardiovasmentioning

confidence: 99%

Vitamin D and Cardiovascular Disease

Norman¹,

Powell

2014

Circulation Research

442

353

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“…In particular, vitamin D inhibits T helper-1 (Th1) lymphocytes and the production of Th1 cytokines such as interleukin (IL)-2, interferon gamma, and tumor necrosis factor alpha (13). Moreover, vitamin D reduces the level of other proinflammatory cytokines such as IL-6 and IL-17 and up-regulates anti-inflammatory mediators such as IL-4 and IL-10; further, it interferes with the differentiation and survival of dendritic cells (14).…”

Section: Introductionmentioning

confidence: 99%

Low vitamin D status in systemic sclerosis and the impact on disease phenotype

et al. 2016

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Objective: Vitamin D has pleiotropic effects including immunomodulatory, cardioprotective, and antifibrotic properties and is thus able to modulate the three main links in scleroderma pathogenesis. The aim of the study was to evaluate the level of vitamin D in patients with systemic sclerosis and to analyze the associations between the concentration of vitamin D and the features of systemic sclerosis.Material and Methods: Fifty-one consecutive patients were evaluated for visceral involvement, immunological profile, activity, severity scores, and quality of life. The vitamin D status was evaluated by measuring the 25hydroxy-hydroxyvitamin D serum levels. Results:The mean vitamin D level was 17.06±9.13 ng/dL. Only 9.8% of the patients had optimal vitamin D levels; 66.66% of them had insufficient 25(OH)D levels, while 23.52% had deficient levels. No correlation was found between vitamin D concentration and age, sex, autoantibody profile, extent of skin involvement, or vitamin D supplementation. Vitamin D levels were correlated with the diffusing capacity of the lung for carbon monoxide (p=0.019, r=0.353), diastolic dysfunction (p=0.033, r=−0.318), digital contractures (p=0.036, r=−0.298), and muscle weakness (p=0.015, r=−0.377) and had a trend for negative correlation with pulmonary hypertension (p=0.053, r=−0.29).Conclusion: Low levels of vitamin D are very common in systemic sclerosis. Poor vitamin status seems to be related with a more aggressive disease with multivisceral and severe organ involvement, especially pulmonary and cardiac involvement.

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“…[33,34] Vitamin D also has a role in reducing the production of proinflammatory cytokines and chemokines. [35][36][37][38] Serum levels of vitamin D have been associated with muscle strength and fat mass, [39] with muscle atrophy in the elderly, [40] and with fatigue and muscle strength in patients with lupus erythematosus. [41] Vitamin D deficiency has been associated with the risk and the severity of diseases, including cancer, cardiovascular disease, sarcopenia, osteoarthritis, and infections.…”

Section: Introductionmentioning

confidence: 99%

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

et al. 2012

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Background and Objective: In patients with advanced cancer, cachexia correlates with low performance status and poor quality of life. In addition, cachexia may be associated with reduced response to chemoradiotherapy and a poor prognosis in cancer patients. Nearly all forms of cachexia are closely associated with chronic inflammation and elevated levels of inflammatory and pro-inflammatory circulating factors, including C-reactive protein (CRP), which is considered a valid laboratory and clinical marker. Among the different pathways involved in the production of inflammatory cytokines and chemokines, the vitamin Dvitamin D receptor (VDR) axis plays a fundamental role.In this study, we explore the possible association between CRP and key factors pertaining to the vitamin D axis -in particular, VDR gene polymorphisms -in cancer patients with cachexia. Although certain tumor types are more commonly associated with cachexia, even within the same tumor type there are significant differences in the extent and duration of cachexia. Such variations may be due to polymorphisms of the VDR gene that could lead to cachexia-prone genotypes or to cachexia-resistant genotypes. Identification of such genotypes could be very helpful in the management of cancer patients. Methods: Forty-three cancer patients were recruited by the Nutritional Unit of the Prato Hospital. Data on age, gender, type of cancer, stage of cancer, and nutritional assessment, as well as transferrin, ferritin, albumin, and CRP levels, were collected. Genomic DNA was extracted from peripheral blood leukocytes and amplified by polymerase chain reaction. BsmI, ApaI, TaqI, and FokI polymorphisms of the VDR gene were investigated using the respective restriction enzymes. For the different VDR polymorphisms, the absence or presence of the restriction sites were designated with capital or small letters, respectively. For example, for the BsmI polymorphism, the presence of the undigested fragment identified the B allele, whereas the presence of the digested fragment identified the b allele. Results: Cancer patients with cachexia have higher CRP levels compared with non-cachectic cancer patients, independently from the genotype. In cachectic patients, the presence of specific VDR BsmI and TaqI alleles was associated with higher CRP levels. In particular, the VDR b and T alleles were more frequent in cachectic cancer patients with elevated CRP levels than in cachectic patients with normal CRP levels. Conclusion: From these results, we hypothesize that there is an association between BsmI and TaqI VDR gene polymorphisms and the cachectic syndrome. In particular, we propose that in cancer patients, the concomitance of b and T alleles with elevated CRP levels may represent an early clinical predictor for the development of a more aggressive form of cachexia.

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Vitamin D3 down-regulates intracellular Toll-like receptor 9 expression and Toll-like receptor 9-induced IL-6 production in human monocytes

Cited by 157 publications

References 11 publications

Vitamin D and Cardiovascular Disease

Vitamin D and Cardiovascular Disease

Low vitamin D status in systemic sclerosis and the impact on disease phenotype

C-Reactive Protein Levels and Vitamin D Receptor Polymorphisms as Markers in Predicting Cachectic Syndrome in Cancer Patients

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