Calcitriol blunts pro-atherosclerotic parameters through NFκB and p38 in vitro

Y. Talmor, J. Bernheim, O. Klein, J. Green, G. Rashid

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Disturbances in vitamin D3 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-κBα (IκBα), phosphorylated-IκBα (P-IκBα) 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 κB (NFκB)-p65 DNA-binding activity was also decreased by calcitriol. IκBα levels were increased and p-IκBα 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 NFκB 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.

Original languageEnglish
Pages (from-to)548-554
Number of pages7
JournalEuropean Journal of Clinical Investigation
Volume38
Issue number8
DOIs
StatePublished - Aug 2008

Keywords

  • Endothelial cells
  • IL-6
  • MAPK
  • NFκB
  • RAGE
  • Vitamin D

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