Vitamin D Research Today is a free monthly online journal that collates and summarizes the latest research about Vitamin D, including details on sources, melanin, benefits, deficiency, supplements, calcium absorption. | ||||||
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1,25-Dihydroxyvitamin D₃ suppresses inflammation-induced expression of plasminogen activator inhibitor-1 by blocking nuclear factor-κB activation.Chen Y, Kong J, Sun T, Li G, Szeto FL, Liu W, Deb DK, Wang Y, Zhao Q, Thadhani R, Li YC Department of Medicine, Division of Biological Sciences, The University of Chicago, Chicago, IL, USA. Plasminogen activator inhibitor (PAI)-1 is a major fibrinolytic inhibitor. High PAI-1 is associated with increased renal and cardiovascular disease risk. Previous studies demonstrated PAI-1 down-regulation by 1,25-dihydroxyvitamin D₃ (1,25(OH)₂D₃), but the molecular mechanism remains unknown. Here we show that exposure of mouse embryonic fibroblasts to TNFα or LPS led to a marked induction of PAI-1, which was blunted by 1,25(OH)₂D₃, NF-κB inhibitor or p65 siRNA, suggesting the involvement of NF-κB in 1,25(OH)₂D₃-induced repression. In mouse Pai-1 promoter a putative cis-κB element was identified at -299. EMSA and ChIP assays showed that TNF-α increased p50/p65 binding to this κB site, which was disrupted by 1,25(OH)₂D₃. Luciferase reporter assays showed that PAI-1 promoter activity was induced by TNFα or LPS, and the induction was blocked by 1,25(OH)₂D₃. Mutation of the κB site blunted TNFα, LPS or 1,25(OH)₂D₃ effects. 1,25(OH)₂D₃ blocked IκBα degradation and arrested p50/p65 nuclear translocation. In mice LPS stimulated PAI-1 expression in the heart and macrophages, and the stimulation was blunted by pre-treatment with a vitamin D analog. Together these data demonstrate that 1,25(OH)₂D₃ down-regulates PAI-1 by blocking NF-κB activation. Inhibition of PAI-1 production may contribute to the reno- and cardio-protective effects of vitamin D. Published 23 February 2011 in Arch Biochem Biophys, 507(2): 241-7. Articles on Vitamin D published 22 February 2011: Oncoprotein Cot1 represses kinase suppressors of Ras1/2 and 1,25-dihydroxyvitamin D3-induced differentiation of human acute myeloid leukemia cells. J Cell Physiol, 226(5): 1232-40. Metabolites and derivatives of vitamin D are well-known inducers of monocytic differentiation, but the mechanistic basis for their action is not fully elucidated. Here we show that the product of protooncogene Cot1 represses the monocytic phenotype in human acute myeloid leukemia (AML) cells induced to differentiate by 1,25-dihydroxyvitamin D(3) (1,25D), even though the expression of cellular Cot1 increases early in the process of 1,25D-induced differentiation. Interestingly, the expression of ... [Abstract] [Full-text] Articles on Vitamin D published 17 February 2011: Multiple sclerosis prevalence in Ireland: relationship to vitamin D status and HLA genotype. J Neurol Neurosurg Psychiatry, 82(3): 317-22. Articles on Vitamin D published 14 February 2011: Vitamin D serum levels and markers of asthma control in Italian children. J Pediatr, 158(3): 437-41. Articles on Vitamin D published 31 January 2011: Dietary vitamin D intake and serum 25-hydroxyvitamin D level in relation to disease outcomes in head and neck cancer patients. Int J Cancer, 128(7): 1741-6. Low pretreatment vitamin D status has been associated with worsened disease outcomes in patients with cancer at various sites. Its prognostic significance in head and neck cancer (HNC) patients has not been studied. Patients with HNC who participated in a randomized trial were evaluated for: (i) total intake of vitamin D from diet and supplements using a validated food frequency questionnaire (all trial participants, n = 540) and (ii) pretreatment serum 25-hydroxyvitamin D through a ... [Abstract] [Full-text] Vitamin D-effective solar UV radiation, dietary vitamin D and breast cancer risk. Int J Cancer, 128(6): 1425-33. Vitamin D is well known for its important role in calcium and phosphor homeostasis. Recent research suggests that vitamin D also prevent some type of cancers. We studied solar vitamin D effective UV radiation (VD dose), dietary vitamin D, sun-seeking holidays, use of solarium, frequency of sunburn and breast cancer risk in a large population-based cohort study. A total of 41,811 women from the prospective Norwegian Women and Cancer Study, aged 40-70 years at baseline, were followed from ... [Abstract] [Full-text] Meta-analysis of observational studies of serum 25-hydroxyvitamin D levels and colorectal, breast and prostate cancer and colorectal adenoma. Int J Cancer, 128(6): 1414-24. Epidemiological studies have suggested a reduced risk of several cancers associated with high vitamin D status. We performed a systematic review with meta-analyses of observational studies of serum 25-hydroxyvitamin D level and colorectal, breast and prostate cancer and colonic adenoma. The literature of December 2009 was searched without language restriction. The meta-regression analysis was done to compute dose-response effects. Because in case-control studies, serum 25-hydroxyvitamin D level ... [Abstract] [Full-text] Dietary vitamin D intake and serum 25-hydroxyvitamin D level in relation to disease outcomes in head and neck cancer patients. Int J Cancer, 128(7): 1741-6. Low pretreatment vitamin D status has been associated with worsened disease outcomes in patients with cancer at various sites. Its prognostic significance in head and neck cancer (HNC) patients has not been studied. Patients with HNC who participated in a randomized trial were evaluated for: (i) total intake of vitamin D from diet and supplements using a validated food frequency questionnaire (all trial participants, n = 540) and (ii) pretreatment serum 25-hydroxyvitamin D through a ... [Abstract] [Full-text] Vitamin D-effective solar UV radiation, dietary vitamin D and breast cancer risk. Int J Cancer, 128(6): 1425-33. Vitamin D is well known for its important role in calcium and phosphor homeostasis. Recent research suggests that vitamin D also prevent some type of cancers. We studied solar vitamin D effective UV radiation (VD dose), dietary vitamin D, sun-seeking holidays, use of solarium, frequency of sunburn and breast cancer risk in a large population-based cohort study. A total of 41,811 women from the prospective Norwegian Women and Cancer Study, aged 40-70 years at baseline, were followed from ... [Abstract] [Full-text] © 2004-2011 Vitamin D Research Today. All Rights Reserved. |
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