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

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).

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.

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.

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