Anti-inflammatory effect of 1α,25-dihydroxyvitamin D3 in human coronary arterial endothelial cells: Implication for the treatment of Kawasaki disease

Suzuki, Yasuo; Ichiyama, Takashi; Ohsaki, Ayami; Hasegawa, Shunji; Shiraishi, Masaya; Furukawa, Susumu

doi:10.1016/j.jsbmb.2008.12.004

Cited by 73 publications

(53 citation statements)

References 40 publications

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“…Interestingly, Thorand et al observed that the significant inverse association between serum 25(OH)D and incident type 2 diabetes was attenuated after adjustment for IL-6 and other inflammatory markers (Thorand et al 2011). Interestingly, studies in CKD children also showed a significant relationship between 25(OH)D and IL-6 independent of the sIL-6r soluble IL-6 receptor, sgp130 signaling-transducing 130-kDa component, CRP C-reactive protein, TNF-α tumor necrosis factor-α, IL-1Ra IL-1 receptor antagonist, sTNFR1 soluble TNF-α receptor 1, sTNFR2 soluble TNF-α receptor 2, AST aspartate aminotransferase, ALT alanine aminotransferase, PTH parathyroid hormone, ADL activities of daily living, vBMDc cortical volumetric bone mineral density, MMSE Mini-Mental State Examination, CES-D Center for Epidemiologic Studies Depression Scale, CHD coronary heart disease, COPD chronic obstructive pulmonary disease, PAD peripheral arterial disease a Age-adjusted severity of kidney disease (Suzuki et al 2009). Finally, in a cohort from the Baltimore Hip Studies, women aged ≥65 years, 25(OH)D deficient at the time of hip fracture, had higher serum IL-6 levels in the year after fracture (Miller et al 2007).…”

Section: Discussionmentioning

confidence: 99%

“…The molecular mechanisms underlying the relationship between vitamin D and IL-6 could be found in the inhibitory action of vitamin D on both cellular expression and activation of the proinflammatory transcription factor kappa B (NFκB). In this way, vitamin D might regulate the release of the inflammatory cytokine IL-6, which represents a downstream target of NFκB activation (Suzuki et al 2009;Jablonski et al 2011). The antiinflammatory properties of vitamin D could be mediated by vitamin D receptor (VDR) (expressed by many types of immune cells) which is part of the inactivating complex with the nuclear p65 subunit of NFκB (Equils et al 2006;Provvedini et al 1983).…”

Section: Discussionmentioning

confidence: 99%

“…25(OH)D could play a role in signaling-related inflammation through a whole spectrum of underlying mechanisms including the downregulation of the proinflammatory transcription factor kappa B (NFκB) (Suzuki et al 2009). On the contrary, the systemic inflammatory response, occurring after an inflammatory insult, could determine lower 25(OH)D concentration (Louw et al 1992;Gray et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Relationship between vitamin D and inflammatory markers in older individuals

Vita

Lauretani

Bauer

et al. 2014

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In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP)≥10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1β, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1-adjusted for age, sex, and parathyroid hormone (PTH); model 2-including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1±17.1 years±SD. In model 1, AGE (2014) log(25OH-D) was significantly and inversely associated with log(IL-6) (β±SE=−0.11±0.03, p=<0.0001) and log (hsCRP) (β±SE=−0.04±0.02, p=0.04) and positively associated with log(sIL6r) (β±SE=0.11±0.04, p=0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (β±SE=−0.10±0.03, p=0.0001) and positively associated with log(sIL6r) (β±SE=0.11± 0.03, p = 0.004) but not with log(hsCRP) (β ±SE= −0.01±0.03, p=0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Relationship between vitamin D and inflammatory markers in older individuals

Vita

Lauretani

Bauer

et al. 2014

AGE

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“…However, a recent study also recognized a calcium-independent mechanism through a direct effect of vitamin D downregulating the expression of COX-1, which is the major source of endothelium-derived contracting factors, in ECs. AA 36,37 Finally, calcitriol may also act as a vascular protective agent counteracting the deleterious effects of advanced glycation end products on endothelial function. 38 Increased concentrations of glucose and advanced glycation end products acting through its receptor of advanced glycation end products can induce the expression of proinflammatory molecules by ECs.…”

Section: 34mentioning

confidence: 99%

Role of Vitamin D in Atherosclerosis

et al. 2013

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A therosclerosis, the principal cause of cardiovascular diseases (CVDs), is a process that involves a complex interplay among different factors and cell types, including cells of the immune system (T cells, B cells, natural killer cells, monocytes/macrophages, dendritic cells) and cells of the vessel wall (endothelial cells [ECs], vascular smooth muscle cells [VSMCs]). The atherogenic process evolves in different stages, starting from inflammatory endothelial activation/ dysfunction and resulting in plaque vulnerability and rupture. Vitamin D deficiency affects almost 50% of the population worldwide. It has been suggested that this pandemic might contribute to the worldwide increased prevalence of CVD. 9-11Several mechanisms have been proposed to account for this inverse relationship. In addition to its effects exerted on numerous tissues and organs that indirectly participate in the atherosclerosis, vitamin D is directly involved in this systemic inflammatory process.12,13 Vitamin D receptors (VDRs) are present in all cells implicated in atherosclerosis, including ECs, VSMCs, and immune cells. Vitamin D appears to regulate a wide range of physiological and pathological processes like vascular cell growth, migration, and differentiation; immune response modulation; cytokine expression; and inflammatory and fibrotic pathways, all of which play a crucial role, starting from the early stage of endothelial activation/dysfunction to the later stages of the plaque vulnerability and rupture.In this review, we provide current data on the effects of vitamin D on cells directly implicated in atherosclerosis such as ECs, VSMCs, and immune cells (lymphocytes, monocytes, macrophages, etc) with a focus on the underlying molecular mechanisms, which are still largely unknown. We also summarize reports related to the favorable (antiatherogenic) actions of vitamin D in tissues and organs that indirectly participate in the atherogenic process. Finally, we critically discuss clinical studies to assess the protective role of vitamin D and the efficacy of vitamin D and VDR agonists in CVD. Because a comprehensive background is a prerequisite for further discussions of vitamin D-induced effects, we provide a brief description of vitamin D metabolism and mechanism of action. Vitamin D Metabolism and Mechanism of ActionVitamin D is a steroid hormone that comes in 2 forms that differ chemically in their side chain, D 2 and D 3 (Figure 1). Either produced in the skin (D 3 ) from 7-dehydrocholesterol by exposure to ultraviolet-B light or ingested with foods of plant or animal origin (D 2 and D 3 , respectively), vitamin D is biologically inert and requires 2 hydroxylations to form its active metabolite. 10 The first hydroxylation is constitutive and takes place in the liver by vitamin D-25-hydroxylase to form 25(OH)D. The second hydroxylation is catalyzed by 25(OH) D-1aOHase (CYP27B1) to form the biologically active form of vitamin D, 1,25(OH) 2 D (calcitriol; see Figure 1). This latter 1a-hydroxylation of 25(OH)D takes place in most tiss...

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“…For example, expression of VDR was observed in the human coronary arterial endothelial cells, and 1a,25-(OH) 2 D 3 significantly inhibited the NFjB activation in the cells. 31 In human umbilical vein endothelial cells, the increase of VCAM-1 and ICAM-1 induced by TNF-a were inhibited by 1a,25-(OH) 2 D 3 . 32 The present study first showed that the active form of vitamin D directly influences BBB endothelial cells through the upregulation of tight junction proteins and downregulation of cell adhesion molecules under TNF-a stimulation.…”

Section: Discussionmentioning

confidence: 93%

Active form of vitamin D directly protects the blood–brain barrier in multiple sclerosis

Takahashi

Maeda

Sano

et al. 2017

Clinical & Exp Neuroim

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Objectives The active form of vitamin D, 1a, 2 D 3 ), is reported to have protective effects for multiple sclerosis (MS), but the precise mechanisms of this effect on MS remain unclear. We hypothesized that 1a,25-(OH) 2 D 3 has protective effects on the blood-brain barrier (BBB) in MS. Methods The expression of vitamin D receptor in a human brain microvascular endothelial cell line (HBMEC) was examined. The effects of 1a,25-(OH) 2 D 3 on HBMEC after stimulation with tumor necrosis factor-a were observed. In addition, we assessed the effects of sera from MS patients, including those in the acute and stable phase of relapse-remitting MS or secondary progressive MS, on the BBB property in the presence or absence of 1a,25-(OH) 2 D 3 . Results HBMEC were found to express the vitamin D receptor at both the mRNA and protein level. Pretreatment of HBMEC with 1a,25-(OH) 2 D 3 attenuated the decrease of zonula occludens-1 and claudin-5, and the increase of intercellular adhesion molecule-1 (ICAM-1) induced by tumor necrosis factor-a. In addition, nuclear factor kappa B activation mediated by tumor necrosis factor-a was decreased after incubation with the activated vitamin D. Furthermore, incubation with 1a,25-(OH) 2 D 3 attenuated the increase of vascular cell adhesion molecule-1 and anti-phospho-nuclear factor kappa B in HBMEC after exposure to sera from patients with relapse-remitting MS and secondary progressive MS, and restored the decrease of zonula occludens-1 and claudin-5 in HBMEC after incubation with sera from the acute phase of relapse-remitting MS patients. Conclusions Treatment with 1a,25-(OH) 2 D 3 prevents BBB disruption caused by both relapse-remitting MS and secondary progressive MS sera through upregulation of tight junction proteins and downregulation of cell adhesion molecules in HBMEC, suggesting that 1a,25-(OH) 2 D 3 might have the direct protective effects on the fragile BBB in MS patients.

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Anti-inflammatory effect of 1α,25-dihydroxyvitamin D3 in human coronary arterial endothelial cells: Implication for the treatment of Kawasaki disease

Cited by 73 publications

References 40 publications

Relationship between vitamin D and inflammatory markers in older individuals

Relationship between vitamin D and inflammatory markers in older individuals

Role of Vitamin D in Atherosclerosis

Active form of vitamin D directly protects the blood–brain barrier in multiple sclerosis

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