Aspirin inhibits tumor necrosis factor-alpha-stimulated fractalkine expression in human umbilical vein endothelial cells.

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Jiang DQ, Liu H, Zhang SB, Zhang XL

Aspirin inhibits tumor necrosis factor-alpha-stimulated fractalkine expression in human umbilical vein endothelial cells.

Chin Med J (Engl). 2009 May 20;122(10):1147-53.

PubMed ID

19493461 [ View in PubMed

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Abstract

BACKGROUND: Fractalkine is an important chemokine mediating local monocyte accumulation and inflammatory reactions in the vascular wall. Aspirin inhibits inflammatory cytokine expression closely related to atherosclerosis through the way independent of platelet and cyclooxygenase (COX). There has been no report about the effect of aspirin on fractalkine expression. We aimed to determine the fractalkine expression in human umbilical vein endothelial cell (HUVEC) stimulated by tumor necrosis factor (TNF)-alpha and the effect of aspirin intervention. METHODS: Six of 8 HUVEC groups received either different concentrations of aspirin (0.02, 0.2, 1.0, 5.0 mmol/L) or 40 micromol/L pyrrolidinecarbodithioc acid (PDTC) or 0.5 micromol/L NS-398. The other two groups were negative control and positive control (TNF-alpha-stimulated). After being incubated for 24 hours, cells of the 8 groups except the negative control one were stimulated with TNF-alpha (4 ng/ml) for another 24 hours. After that, the cells were collected for RNA isolation and protein extraction. RESULTS: Both mRNA and protein expressions of fractalkine in HUVEC were upregulated by 4 ng/ml TNF-alpha stimulation. Aspirin inhibited fractalkine expression in a dose-dependent manner at mRNA and protein levels. Nuclear factor-kappa B inhibitor, PDTC, effectively decreased the fractalkine expression. Fractalkine expression was not influenced by COX-2 selective inhibitor NS-398. COX-1 protein expression was not changed by either TNF-alpha stimulation or aspirin, PDTC, NS-398 intervention. Both mRNA and protein expression of COX-2 in HUVEC were upregulated by 4 ng/ml TNF-alpha stimulation. Aspirin decreased COX-2 expression in a dose-dependent manner at mRNA and protein levels. CONCLUSIONS: TNF-alpha-stimulated fractalkine expression is suppressed by aspirin in a dose-dependent manner through the nuclear factor-kappa B p65 pathway.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Acetylsalicylic acid	Tumor necrosis factor-inducible gene 6 protein	Protein	Humans	Unknown	Inhibitor Downregulator	Details

Pharmaco-transcriptomics

Drug	Drug Groups	Gene	Gene ID	Change	Interaction	Chromosome
Acetylsalicylic acid	Approved Vet Approved	PTGS1	5742	downregulated	Aspirin results in decreased expression of PTGS1 mRNA	9q33.2