Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.

Antioxidants have been proposed to be anti-atherosclerotic agents; however, the mechanisms underlying their beneficial effects are poorly understood. We have examined the effect of alpha-tocopherol (alpha-tcp) on one cellular event in atherosclerotic plaque development, monocyte adhesion to stimulat...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلفون الرئيسيون: Faruqi, R, de la Motte, C, DiCorleto, P E
التنسيق: مقال
اللغة:en
منشور في: 1994
الموضوعات:
Research Article
الوصول للمادة أونلاين:https://ncbi.nlm.nih.gov/pmc/articles/PMC296135/
https://ncbi.nlm.nih.gov/pubmed/7518838
الوسوم: إضافة وسم
لا توجد وسوم, كن أول من يضع وسما على هذه التسجيلة!
id pubmed-296135
record_format dspace
spelling pubmed-2961352004-07-07 Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells. Faruqi, R de la Motte, C DiCorleto, P E J Clin Invest Research Article Antioxidants have been proposed to be anti-atherosclerotic agents; however, the mechanisms underlying their beneficial effects are poorly understood. We have examined the effect of alpha-tocopherol (alpha-tcp) on one cellular event in atherosclerotic plaque development, monocyte adhesion to stimulated endothelial cells (ECs). Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion: IL-1 (10 ng/ml), LPS (10 ng/ml), thrombin (30 U/ml), or PMA (10 nM). Agonist-induced monocytic cell adhesion, but not basal adhesion, was inhibited in a time- and concentration-dependent manner by alpha-tcp. The IC50 of alpha-tcp on an IL-1-induced response was 45 microM. The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system. Probucol (50 microM) and N-acetylcysteine (20 mM) also inhibited agonist-induced monocytic cell adhesion; whereas, several other antioxidants had no significant effect. Protein kinase C (PKC) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of PKC substrates was observed. Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC. Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this transcription factor after cytokine stimulation. It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL--a putative triggering molecule in the atherosclerotic process. Our results point to a novel alternative mechanism of action of alpha-tcp. 1994-08 /pmc/articles/PMC296135/ /pubmed/7518838 Text en
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Research Article
spellingShingle Research Article
Faruqi, R
de la Motte, C
DiCorleto, P E
Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.
description Antioxidants have been proposed to be anti-atherosclerotic agents; however, the mechanisms underlying their beneficial effects are poorly understood. We have examined the effect of alpha-tocopherol (alpha-tcp) on one cellular event in atherosclerotic plaque development, monocyte adhesion to stimulated endothelial cells (ECs). Human umbilical vein ECs were pretreated with alpha-tcp before stimulation with known agonists of monocyte adhesion: IL-1 (10 ng/ml), LPS (10 ng/ml), thrombin (30 U/ml), or PMA (10 nM). Agonist-induced monocytic cell adhesion, but not basal adhesion, was inhibited in a time- and concentration-dependent manner by alpha-tcp. The IC50 of alpha-tcp on an IL-1-induced response was 45 microM. The inhibition correlated with a decrease in steady state levels of E-selectin mRNA and cell surface expression of E-selectin which is consistent with the ability of a monoclonal antibody to E-selectin to inhibit monocytic cell adhesion in this system. Probucol (50 microM) and N-acetylcysteine (20 mM) also inhibited agonist-induced monocytic cell adhesion; whereas, several other antioxidants had no significant effect. Protein kinase C (PKC) does not appear to play a role in the alpha-tcp effect since no suppression of phosphorylation of PKC substrates was observed. Activation of the transcription factor NF-kappa B is reported to be necessary but not sufficient for E-selectin expression in EC. Electrophoretic mobility shift assays failed to show an alpha-tcp-induced decrease in activation of this transcription factor after cytokine stimulation. It has been hypothesized that alpha-tcp acts as an anti-atherosclerotic molecule by inhibiting generation of oxidized LDL--a putative triggering molecule in the atherosclerotic process. Our results point to a novel alternative mechanism of action of alpha-tcp.
author Faruqi, R
de la Motte, C
DiCorleto, P E
author_facet Faruqi, R
de la Motte, C
DiCorleto, P E
author_sort Faruqi, R
title Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.
title_short Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.
title_full Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.
title_fullStr Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.
title_full_unstemmed Alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.
title_sort alpha-tocopherol inhibits agonist-induced monocytic cell adhesion to cultured human endothelial cells.
publishDate 1994
url https://ncbi.nlm.nih.gov/pmc/articles/PMC296135/
https://ncbi.nlm.nih.gov/pubmed/7518838
_version_ 1759374622053105664

مواد مشابهة