Epicatechin, catechin, and dimeric procyanidins inhibit PMA-induced NF-kappaB 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-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.
Mackenzie
Gerardo G
GG
Departamento de Química BiolOgica, Instituto de Química y Fisicoquímica Biológicas, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Farmacia y Bioquímica, Buenos Aires, Argentina.
Carrasquedo
Fernando
F
Delfino
José M
JM
Keen
Carl L
CL
Fraga
César G
CG
Oteiza
Patricia I
PI
D044946:Biflavonoids; D001665:Binding Sites; D002392:Catechin / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016384:Consensus Sequence; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D016328:NF-kappa B / Q000378:metabolism*; D010084:Oxidation-Reduction; D044945:Proanthocyanidins; D013601:T-Lymphocytes / Q000187:drug effects* / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors
D044946:Biflavonoids; D016328:NF-kappa B; D044945:Proanthocyanidins; C017674:procyanidin; D002392:Catechin; D004247:DNA; D013755:Tetradecanoylphorbol Acetate