Febuxostat Attenuates the Induction of Vascular Cell Adhesion Protein 1 by TNF-α in Human Umbilical Vein Endothelial Cells

Pharmacology. 2021;106(3-4):218-224. doi: 10.1159/000511278. Epub 2020 Nov 11.

Abstract

In a randomized trial, higher all-cause and cardiovascular mortality was observed in treatment with febuxostat than with allopurinol in patients with coexisting gout and serious cardiovascular conditions. In this study, we focus on an intervention of febuxostat or allopurinol as an anti-inflammatory treatment to reduce the transcription of nuclear factor-kappa B (NF-κB) and production of relevant inflammatory factors. We evaluated the effect of febuxostat on vascular cell adhesion protein 1 (VCAM-1) induction in cultured human umbilical vein endothelial cells (HUVECs). Cells were exposed to tumor necrosis factor (TNF)-α (10 ng/mL) treatment for 24 h. Febuxostat or allopurinol (0.1-100 μM) was added to the bath medium 15 min before TNF-α treatment. VCAM-1 levels in HUVECs increased after 24-h TNF-α treatment (n = 4). Febuxostat and allopurinol significantly suppressed VCAM-1 induced by treatment with TNF-α in a dose-dependent manner (p < 0.05, n = 4). Furthermore, these drugs suppressed the NF-κB protein levels in the nucleus 4 h after TNF-α treatment (n = 3 or 4). Our results suggest that TNF-α induces VCAM-1 production via NF-κB, which can be blocked by febuxostat or allopurinol. The effect of febuxostat treatment on cardiovascular events may be associated with protection against the infiltration of lymphocytes or monocytes through VCAM-1 induction in inflamed endothelial cells such as arterial sclerosis.

Keywords: Febuxostat; Human umbilical vein endothelial cell; Vascular cell adhesion protein 1.

Publication types

  • News

MeSH terms

  • Allopurinol / pharmacology
  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Febuxostat / pharmacology*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • I-kappa B Proteins / metabolism
  • NF-kappa B p50 Subunit / metabolism
  • Protein Transport
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / biosynthesis*
  • Vascular Cell Adhesion Molecule-1 / genetics

Substances

  • Anti-Inflammatory Agents
  • I kappa B beta protein
  • I-kappa B Proteins
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Febuxostat
  • Allopurinol