Epicatechin, catechin, and dimeric procyanidins inhibit PMA-induced NF-κB activation at multiple steps in Jurkat T cells

The capacity of the flavan-3-ols [(-)-epicatechin (EC) and (+)-catechin (CT)] and a B dimeric procyanidin (DP-B) to modulate phorbol 12-myristate 13-acetate (PMA)-induced NF-kappa B activation in Jurkat T cells was investigated. The classic PMA-triggered increase in cell oxidants was prevented when cells were preincubated for 24 h with EC, CT, or DP-B (1.7-17.2 mu M). PMA induced the phosphorylation of IKK beta and the subsequent degradation Of I kappa B alpha: These events were inhibited in cells pretreated with the flavonoids. PMA induced a 4.6-fold increase in NF-kappa B nuclear binding activity in control cells. Pretreatment with EC, CT, or DP-B decreased PMA-induced NF-kappa B binding activity and the transactivation of the NF-kappa B-driven gene IL-2. EC, CT, and DP-B inhibited, in vitro, NF-kappa B binding to its DNA consensus sequence, but they had no effect on the binding activity of CREB or OCT-1. Thus, EC, CT, or DP-B can influence the immune response by modulating NF-kappa B activation. This modulation can occur at early (regulation of oxidant levels, IKK activation) as well as late (binding of NF-kappa B to DNA) stages of the NF-kappa B activation cascade. A model is presented for possible interactions between DP-B and NF-kappa B proteins, which could lead to the inhibition of NF-kappa B binding to kappa B sites.