Calcitriol inhibits TNF-α-induced inflammatory cytokines in human trophoblasts

Díaz, Lorenza; Noyola-Martínez, Nancy; Barrera, David; Hernández, Guillermo; Avila, Euclides; Halhali, Ali; Larrea, Fernando

doi:10.1016/j.jri.2009.02.005

Cited by 164 publications

(138 citation statements)

References 39 publications

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“…Coexpression of the receptor for 1,25(OH) 2 D 3 (vitamin D receptor [VDR]) in both decidua (9) and trophoblast (10) suggests that 1,25 (OH) 2 D 3 produced by the placenta may function in an autocrine or paracrine fashion. In support of this, recent studies by our group and others have shown that autocrine metabolism of 25OHD 3 to 1,25(OH) 2 D 3 promotes antibacterial and anti-inflammatory responses in maternal decidua (11) and fetal trophoblast (12,13). Such immunomodulatory actions of vitamin D are likely to be compromised under conditions of low maternal 25OHD 3 status, with potentially detrimental consequences for placental physiology.…”

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confidence: 76%

Vitamin D and the Regulation of Placental Inflammation

Liu

Kaplan

Lagishetty

et al. 2011

The Journal of Immunology

183

118

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The vitamin D-activating enzyme 1α-hydroxylase (CYP27B1) and vitamin D receptor (VDR) support anti-inflammatory responses to vitamin D in many tissues. Given the high basal expression of CYP27B1 and VDR in trophoblastic cells from the placenta, we hypothesized that anti-inflammatory effects of vitamin D may be particularly important in this organ. Pregnant wild type (WT) mice i.p. injected with LPS showed elevated expression of mouse Cyp27b1 (4-fold) and VDR (6-fold). Similar results were also obtained after ex vivo treatment of WT placentas with LPS. To assess the functional impact of this, we carried out ex vivo studies using placentas −/− for fetal (trophoblastic) Cyp27b1 or VDR. Vehicle-treated −/− placentas showed increased expression of IFN-γ and decreased expression of IL-10 relative to +/+ placentas. LPS-treated −/− placentas showed increased expression of TLR2, IFN-γ, and IL-6. Array analyses identified other inflammatory factors that are dysregulated in Cyp27b1−/− versus Cyp27b1+/+ placentas after LPS challenge. Data highlighted enhanced expression of IL-4, IL-15, and IL-18, as well as several chemokines and their receptors, in Cyp27b1−/− placentas. Similar results for IL-6 expression were observed with placentas −/− for trophoblastic VDR. Finally, ex vivo treatment of WT placentas with the substrate for Cyp27b1, 25-hydroxyvitamin D3, suppressed LPS-induced expression of IL-6 and the chemokine Ccl11. These data indicate that fetal (trophoblastic) vitamin D plays a pivotal role in controlling placental inflammation. In humans, this may be a key factor in placental responses to infection and associated adverse outcomes of pregnancy.

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mentioning

confidence: 76%

Vitamin D and the Regulation of Placental Inflammation

Liu

Kaplan

Lagishetty

et al. 2011

The Journal of Immunology

183

118

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“…We conducted our experiments with 0.1 or 10 nM vitamin D 3 as described in several publications (5,18), approximating physiologic vitamin D 3 serum concentrations in pregnant and nonpregnant women (0.1 nM; Refs. 18,24).…”

Section: Discussionmentioning

confidence: 99%

“…18,24). While the placenta produces ϳ50% of the circulating vitamin D 3 (16) of pregnant women, we assume higher placental vitamin D 3 levels and included 10 nM vitamin D 3 in our experimental setting to simulate local placental conditions.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D improves the angiogenic properties of endothelial progenitor cells

Grundmann

Haidar

Placzko

et al. 2012

American Journal of Physiology-Cell Physiology

137

113

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The main pathogenic feature of preeclampsia is maternal endothelial dysfunction that results from impaired angiogenesis and reduced endothelial repair capacity. In addition, preeclampsia risk is associated with vitamin D deficiency. We hypothesized that vitamin D3 stimulates proangiogenic properties of endothelial colony-forming cells (ECFCs). ECFCs were obtained and cultured from cord blood and characterized by immunocytochemistry and flow cytometry. Proliferation, total length of tubule formation on Matrigel, expression of VEGF mRNA, and pro-matrix metalloproteinases (MMP)-2 activity were assessed after treatment of ECFCs with vitamin D 3. Specificity of the observed effects was tested by blocking the vitamin D receptor (VDR) or the VEGF signaling pathway. ECFCs treated with 10 nM vitamin D3 showed a 1.27 times higher tubule formation compared with vehicle-treated controls (1.27 Ϯ 0.19) as well as a 1.36 times higher proliferation rate (1.36 Ϯ 0.06). Vitamin D3 induced pro-MMP-2 activity (1.29 Ϯ 0.17) and VEGF mRNA levels (1.74 Ϯ 0.73) in ECFCs. VDR blocking by pyridoxal-5-phosphate (0.73 Ϯ 0.19) or small interfering RNA (0.75 Ϯ 0.17) and VEGF inhibition by Su5416 (0.56 Ϯ 0.16) or soluble fms-like tyrosine kinase-1 (0.7 Ϯ 0.14) reduced tubule formation and pro-MMP-2 activity (pyridoxal-5-phosphate: 0.84 Ϯ 0.09; Su5416: 0.79 Ϯ 0.11; or sFlt: 0.88 Ϯ 0.13). This effect was neutralized by vitamin D3. Consequently, vitamin D3 significantly promoted angiogenesis in ECFCs in vitro possibly due to an increase in VEGF expression and pro-MMP-2 activity. Since angiogenesis is a crucial feature in the pathophysiology of preeclampsia these findings could explain the positive influence of vitamin D3 in reducing preeclampsia risk. vitamin D; preeclampsia; ECFC; angiogenesis; VEGF VITAMIN D, PRIMARILY KNOWN for its important role in calcium homeostasis and bone metabolism, influences the cardiovascular system through unclear mechanisms (33). Vitamin D deficiency is associated with increased all-cause and cardiovascular disease mortality, coronary heart disease, and various cardiovascular risk factors (33).Preeclampsia, a pregnancy-specific disorder that affects 3-7% of all pregnancies, is a major cause of maternal and fetal morbidity and mortality (43) and is associated with an increased risk for cardiovascular events later in life (6). Endothelial dysfunction underlies the hypertension, proteinuria, and multiorgan damage that occur during preeclampsia. The mechanisms that contribute to the disturbed endothelial homeostasis in the pathophysiology of preeclampsia remain unclear (41,46). Compared with normal pregnancies, preeclampsia is characterized by marked changes in vitamin D and calcium metabolism (3). Epidemiological studies have demonstrated an association between low maternal vitamin D levels and the incidence of preeclampsia (23, 27) and suggest vitamin D deficiency to be an independent risk factor for the development of preeclampsia (7). Moreover, vitamin D supplementation studies also showed protective effects on pr...

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“…Учитывая эти иммунные эффекты, было вы-сказано предположение, что витамин D может выступать в качестве иммунного регулятора во время имплантации и играть важную роль в репродуктивной функции. В ранние сроки бе-ременности трофобласт производит и отвечает на воздействие витамина D, который оказыва-ет местную противовоспалительную реакцию и индуцирует рост децидуальной ткани, необ-ходимой для успешной беременности [29].…”

Section: роль витамина D в регуляции репродуктивной функцииunclassified

The role of vitamin D in the pathogenesis of genital endometriosis

Denisova

Yarmolinskaya

2017

Z.akus.zen.bolezn

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The influence of vitamin D on the women’s health is undeniable. Here we review the modern classification of vitamin D forms and receptors, the current understanding of genomic and non-genomic regulation pathways of vitamin D synthesis. It was found that a vitamin D deficiency related to the development of many diseases, negative impact on reproductive function and pregnancy outcomes. Nowadays, vitamin D is concerned as a prohormone that has multiple effects. Special attention is given to the role of vitamin D in the pathogenesis of genital endometriosis. It is known that vitamin D has anti-inflammatory, antiproliferative and immunomodulating effects, which allow it to be considered as a forward-looking target therapy in endometriosis.

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Calcitriol inhibits TNF-α-induced inflammatory cytokines in human trophoblasts

Cited by 164 publications

References 39 publications

Vitamin D and the Regulation of Placental Inflammation

Vitamin D and the Regulation of Placental Inflammation

Vitamin D improves the angiogenic properties of endothelial progenitor cells

The role of vitamin D in the pathogenesis of genital endometriosis

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