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Given the central role of the transcription factor NF-kappaB in inflammation, molecules that can inhibit NF-kappaB are being actively investigated. The present work characterize potential interactions between dimeric procyanidins [B-type (B1 and B2) and A-type (A1 and A2)] and NF-kappaB proteins. B1 and B2, inhibited tumor necrosis factor alpha (TNFalpha)- and phorbol 12-myristate 13-acetate (PMA)-induced transactivation of NF-kappaB-driven genes and the increase of NF-kappaB-DNA nuclear binding in Jurkat T cells. B1 and B2, added in vitro to nuclear fractions, inhibited NF-kappaB binding to its DNA consensus sequence. B1 and B2 prevented the binding of RelA and p50 recombinant proteins to its DNA consensus sequence. All these effects were not observed with A1 and A2. Putative molecular models for possible interactions of B1, B2, A1 and A2, with NF-kappaB proteins were constructed, indicating that B-type dimeric procyanidins have higher possibilities of chemical interactions with NF-kappaB than A-type dimeric procyanidins. The results support the concept that B-type dimeric procyanidins can provide anti-inflammatory benefits due to their ability to reduce NF-kappaB binding to the DNA.

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-kappaB 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 microM). PMA induced the phosphorylation of IKKbeta and the subsequent degradation of IkappaBalpha. These events were inhibited in cells pretreated with the flavonoids. PMA induced a 4.6-fold increase in NF-kappaB nuclear binding activity in control cells. Pretreatment with EC, CT, or DP-B decreased PMA-induced NF-kappaB binding activity and the transactivation of the NF-kappaB-driven gene IL-2. EC, CT, and DP-B inhibited, in vitro, NF-kappaB 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-kappaB activation. This modulation can occur at early (regulation of oxidant levels, IKK activation) as well as late (binding of NF-kappaB to DNA) stages of the NF-kappaB activation cascade. A model is presented for possible interactions between DP-B and NF-kappaB proteins, which could lead to the inhibition of NF-kappaB binding to kappaB sites.