Inhibition of mycophenolic acid on NF-kappaB activity in human endothelial cells

Acta Pharmacol Sin. 2002 Jul;23(7):649-53.

Abstract

Aim: To examine the effect of mycophenolic acid (MPA) on the activity of nuclear factor-kappaB (NF-kappaB) and its inhibitor (IkappaBalpha) in 4-phorbal-12-myristate-13-acetate (PMA) stimulated and non-stimulated human umbilical vein endothelial cells (HUVEC).

Methods: MPA at various concentrations were applied to cultured HUVEC, pre-incubated or not pre-incubated with PMA (100 microg/L for 30 min). The activity of NF-kappaB in endothelial cells was measured with electrophoretic mobility shift assays (EMSA), and IkappaBalpha protein levels were detected by Western blot method.

Results: Incubation with PMA was found to result in rapid increment of NF-kappaB activity in cultured HUVEC. MPA treatment decreased the activities of NF-kappaB, both in PMA treatment and un-treatment HUVEC. Protein level of IkappaBalpha was decreased in PMA-treatment HUVEC. MPA treatment increased IkappaBalpha protein levels in both PMA-treatment and un-treatment HUVEC.

Conclusion: MPA is a potent inhibitor of NF-kappaB activation in endothelial cells, which might explain its beneficial effect in endothelial cells.

MeSH terms

  • Cells, Cultured
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / metabolism*
  • Humans
  • I-kappa B Proteins / metabolism
  • Mycophenolic Acid / pharmacology*
  • NF-KappaB Inhibitor alpha
  • NF-kappa B / metabolism*
  • Tetradecanoylphorbol Acetate / pharmacology
  • Umbilical Veins / cytology

Substances

  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • NF-KappaB Inhibitor alpha
  • Mycophenolic Acid
  • Tetradecanoylphorbol Acetate