Dimeric procyanidins are inhibitors of NF-κB-DNA binding

Gerardo Mackenzie, Jose M. Delfino, Carl L Keen, Cesar G. Fraga, Patricia I. Oteiza

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Given the central role of the transcription factor NF-κB in inflammation, molecules that can inhibit NF-κB 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-κB proteins. B1 and B2, inhibited tumor necrosis factor α (TNFα)- and phorbol 12-myristate 13-acetate (PMA)-induced transactivation of NF-κB-driven genes and the increase of NF-κB-DNA nuclear binding in Jurkat T cells. B1 and B2, added in vitro to nuclear fractions, inhibited NF-κB 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-κB proteins were constructed, indicating that B-type dimeric procyanidins have higher possibilities of chemical interactions with NF-κB 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-κB binding to the DNA.

Original languageEnglish (US)
Pages (from-to)1252-1262
Number of pages11
JournalBiochemical Pharmacology
Volume78
Issue number9
DOIs
StatePublished - Nov 1 2009

Fingerprint

B-Form DNA
Proanthocyanidins
varespladib methyl
DNA sequences
Consensus Sequence
Molecular Models
Jurkat Cells
T-cells
Recombinant Proteins
Transcriptional Activation
Acetates
Anti-Inflammatory Agents
Transcription Factors
Tumor Necrosis Factor-alpha
Genes
Inflammation
T-Lymphocytes
Molecules
DNA
IgA receptor

Keywords

  • Flavonoids
  • Immune response
  • Inflammation
  • NF-κB
  • Procyanidins

ASJC Scopus subject areas

  • Pharmacology
  • Biochemistry

Cite this

Mackenzie, G., Delfino, J. M., Keen, C. L., Fraga, C. G., & Oteiza, P. I. (2009). Dimeric procyanidins are inhibitors of NF-κB-DNA binding. Biochemical Pharmacology, 78(9), 1252-1262. https://doi.org/10.1016/j.bcp.2009.06.111

Dimeric procyanidins are inhibitors of NF-κB-DNA binding. / Mackenzie, Gerardo; Delfino, Jose M.; Keen, Carl L; Fraga, Cesar G.; Oteiza, Patricia I.

In: Biochemical Pharmacology, Vol. 78, No. 9, 01.11.2009, p. 1252-1262.

Research output: Contribution to journalArticle

Mackenzie, G, Delfino, JM, Keen, CL, Fraga, CG & Oteiza, PI 2009, 'Dimeric procyanidins are inhibitors of NF-κB-DNA binding', Biochemical Pharmacology, vol. 78, no. 9, pp. 1252-1262. https://doi.org/10.1016/j.bcp.2009.06.111
Mackenzie, Gerardo ; Delfino, Jose M. ; Keen, Carl L ; Fraga, Cesar G. ; Oteiza, Patricia I. / Dimeric procyanidins are inhibitors of NF-κB-DNA binding. In: Biochemical Pharmacology. 2009 ; Vol. 78, No. 9. pp. 1252-1262.
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