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Calcitriol blunts pro-atherosclerotic parameters through NFkappaB and p38 in vitro.
Eur J Clin Invest. 2008 Aug; 38(8):548-54.EJ

Abstract

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.

Authors+Show Affiliations

Renal Physiology Laboratory, Department of Nephrology and Hypertension, Meir Medical Centre, Kfar-Saba, Israel.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18717824

Citation

Talmor, Y, et al. "Calcitriol Blunts Pro-atherosclerotic Parameters Through NFkappaB and P38 in Vitro." European Journal of Clinical Investigation, vol. 38, no. 8, 2008, pp. 548-54.
Talmor Y, Bernheim J, Klein O, et al. Calcitriol blunts pro-atherosclerotic parameters through NFkappaB and p38 in vitro. Eur J Clin Invest. 2008;38(8):548-54.
Talmor, Y., Bernheim, J., Klein, O., Green, J., & Rashid, G. (2008). Calcitriol blunts pro-atherosclerotic parameters through NFkappaB and p38 in vitro. European Journal of Clinical Investigation, 38(8), 548-54. https://doi.org/10.1111/j.1365-2362.2008.01977.x
Talmor Y, et al. Calcitriol Blunts Pro-atherosclerotic Parameters Through NFkappaB and P38 in Vitro. Eur J Clin Invest. 2008;38(8):548-54. PubMed PMID: 18717824.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Calcitriol blunts pro-atherosclerotic parameters through NFkappaB and p38 in vitro. AU - Talmor,Y, AU - Bernheim,J, AU - Klein,O, AU - Green,J, AU - Rashid,G, PY - 2008/8/23/pubmed PY - 2008/12/17/medline PY - 2008/8/23/entrez SP - 548 EP - 54 JF - European journal of clinical investigation JO - Eur J Clin Invest VL - 38 IS - 8 N2 - 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. SN - 1365-2362 UR - https://www.unboundmedicine.com/medline/citation/18717824/Calcitriol_blunts_pro_atherosclerotic_parameters_through_NFkappaB_and_p38_in_vitro_ L2 - https://doi.org/10.1111/j.1365-2362.2008.01977.x DB - PRIME DP - Unbound Medicine ER -