Calcitriol blunts pro-atherosclerotic parameters through NFkappaB and p38 in vitro
| Autor: | Rashid G, Janice Green, Y. Talmor, Joelle Bernheim, Osnat Klein |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
MAPK/ERK pathway
Glycation End Products Advanced medicine.medical_specialty Umbilical Veins Calcitriol Clinical Biochemistry Blotting Western Receptor for Advanced Glycation End Products Enzyme-Linked Immunosorbent Assay Biochemistry p38 Mitogen-Activated Protein Kinases Umbilical vein chemistry.chemical_compound Internal medicine polycyclic compounds medicine Humans Receptors Immunologic Cell adhesion Protein kinase A Cells Cultured Inflammation Cell adhesion molecule Interleukin-6 Reverse Transcriptase Polymerase Chain Reaction NF-kappa B Endothelial Cells General Medicine Intercellular Adhesion Molecule-1 Blot Calcium Channel Agonists Endocrinology chemistry Advanced glycation end-product RNA lipids (amino acids peptides and proteins) medicine.drug |
| Zdroj: | European journal of clinical investigation. 38(8) |
| ISSN: | 1365-2362 |
| Popis: | Background Disturbances in vitamin D(3) metabolism are associated with an increased cardiovascular morbidity and mortality. The aim of this study was to assess the effects of calcitriol, the active metabolite of vitamin D3, on pro-atherosclerotic parameters in human umbilical vein cord endothelial cells (HUVEC). Materials and methods Calcitriol at 10(-10) and/or 10(-9) mol L(-1) was given to cultured HUVEC which were either non-stimulated or lipopolysaccharide (LPS) stimulated. Inter cellular adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1, were determined by flow cytometry analysis. The receptor of advanced glycation end product (RAGE) and interleukin-6 (IL-6) mRNA expressions by RT-PCR and IL-6 secretion by enzyme-linked immunosorbent assay (ELISA). Nuclear p65 DNA-binding activity was measured by transcription factor assay kit and the inhibitor-kappaBalpha (IkappaBalpha), phosphorylated-IkappaBalpha (P-IkappaBalpha) and phosphorylated-p38 mitogen-activated protein kinase (MAPK) protein levels were determined by Western blot. Results Calcitriol decreased the adhesion molecules expression, as well as the LPS-induced mRNA expressions of RAGE and IL-6 and LPS induced IL-6 secretion. Furthermore, the LPS induced nuclear factor kappaB (NFkappaB)-p65 DNA-binding activity was also decreased by calcitriol. IkappaBalpha levels were increased and p-IkappaBalpha levels decreased after calcitriol treatment. The increased levels of activated p38 MAPK after LPS treatment were also decreased due to pre-incubation with calcitriol. Conclusions The decreased NFkappaB and p38 activities followed by calcitriol treatment may explain the anti-inflammatory/atherosclerotic properties of calcitriol that were observed previously and were emphasized in this study, demonstrating the inhibitory effect of calcitriol on the pro-inflammatory parameters: adhesion molecules, RAGE and IL-6. |
| Databáze: | OpenAIRE |
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