OPEN IN READ APP
JOURNAL ARTICLE

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

Y Talmor, J Bernheim, O Klein, J Green, G Rashid
European Journal of Clinical Investigation 2008, 38 (8): 548-54
18717824

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.

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
18717824
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"