Background: Low serum levels of 1,25(OH)(2)D(3) (1,25D), have been associated with aggressive biologic behavior of prostate cancer (PCa). In the present study, we examined the effects of 1,25D and its novel, low-calcemic analog ZK191784 (ZK) on matrix metalloproteinases (MMPs), as well as on intercellular adhesion molecule-1 (ICAM-1) protein levels in human PCa cell lines LNCaP and DU-145.
Materials And Methods: Cells were incubated with either vehicle (control), 1,25D or ZK. MMP-2 and MMP-9 activity was determined by gelatin zymography, while ICAM-1 levels were assessed by Western blot analysis and immunocytochemistry.
Results: Compared to the controls, 1,25D and ZK caused a marked dose-dependent decrease in the gelatinolytic activity of the MMPs under study, particularly when ZK was used. Likewise, ICAM-1 was down-regulated in the cells incubated with 1,25D or ZK.
Conclusion: Vitamin D analogs appear to be involved in the regulation of extracellular MMP activity and membrane adhesion molecule expression. Further studies, both in vitro and in vivo, are needed to define their role as potential therapeutic tools.
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Diabetes Metab Syndr Obes
May 2020
Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, Merseyside, UK.
Purpose: Key research findings suggest that attenuating metaflammation in adipose tissue might be a strategic step to prevent the metabolic syndrome and its associated disease outcomes. The anti-inflammatory effects of 1α,25(OH)D have been confirmed in our previous studies, but adverse effects induced at high concentrations restrict its potential clinical translation. Two synthetic 1α,25(OH)D analogs ZK159222 and ZK191784 have manifested promising tissue-specific immunomodulatory actions, but limited data are available on adipose tissue.
View Article and Find Full Text PDFBiochem Biophys Res Commun
September 2018
Institute of Ageing and Chronic Disease, University of Liverpool, William Henry Duncan Building, 6 West Derby Street, Liverpool, L7 8TX, United Kingdom. Electronic address:
Metaflammation in adipose tissue, which is characterized by increased local gene expression and secretion of pro-inflammatory factors, may contribute to the increased risk of metabolic complications in obesity. It has been suggested that IL-1β might induce metaflammation in adipose tissue via modulating the NF-κB signaling pathway. In our study, the mRNA and secretion levels of major pro-inflammatory factors including IL (interleukin)-1β, IL-6, IL-8, MCP (monocyte chemoattractant protein)-1 and RANTES (regulated on activation, normal T cell expressed and secreted) were measured as indicators of the inflammatory profile.
View Article and Find Full Text PDFNeuropharmacology
April 2017
Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Molecular and Applied Biology Research Unit, University of Florence, Viale GB Morgagni 50, 5134 Firenze, Italy; Interuniversitary Miology Institutes, Italy. Electronic address:
Besides its classical function of bone metabolism regulation, 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)D), acts on a variety of tissues including the nervous system, where the hormone plays an important role as neuroprotective, antiproliferating and differentiating agent. Sphingolipids are bioactive lipids that play critical and complex roles in regulating cell fate. In the present paper we have investigated whether sphingolipids are involved in the protective action of 1,25(OH)D We have found that 1,25(OH)D prevents amyloid-β peptide (Aβ(1-42)) cytotoxicity both in differentiated SH-SY5Y human neuroblastoma cells and in vivo.
View Article and Find Full Text PDFFree Radic Biol Med
October 2016
Department of Medicine, University of Florida College of Medicine, Jacksonville, FL, United States.
Endoplasmic reticulum (ER) stress and oxidative stress promote endothelial dysfunction and atherosclerosis. Since vitamin D has been shown in several studies to lower the risk of cardiovascular disease, we examined the effects of vitamin D on ER stress and oxidative stress in endothelial cells. ER stress was measured using the placental secreted alkaline phosphatase assay and oxidative stress was measured by hydroethidine fluorescence.
View Article and Find Full Text PDFJ Crohns Colitis
September 2014
Department of Biomedical, Experimental and Clinical Sciences, University of Florence, Viale Morgagni 50, 50134 Florence, Italy. Electronic address:
Background And Aim: The adhesion molecule expression and matrix metalloproteinases (MMPs) are proposed to be major factors for intestinal injury mediated by T cells in (IBD) and are up-regulated in intestinal mucosa of IBD patients. To investigate the effect of vitamin D derivatives on adhesion molecules and MMPs in colonic biopsies of IBD patients.
Methods: Biopsies from inflamed and non-inflamed tract of terminal ileum and colon and PBMC from the same IBD patients were cultured with or without vitamin D derivatives.
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