Caffeic acid phenethyl ester inhibits T-cell activation by targeting both nuclear factor of activated T-cells and NF-kappaB transcription factors

J Pharmacol Exp Ther. 2004 Mar;308(3):993-1001. doi: 10.1124/jpet.103.060673. Epub 2003 Nov 14.


Caffeic acid phenethyl ester (CAPE), which is derived from the propolis of honeybee hives, has been shown to reveal anti-inflammatory properties. Since T-cells play a key role in the onset of several inflammatory diseases, we have evaluated the immunosuppressive activity of CAPE in human T-cells, discovering that this phenolic compound is a potent inhibitor of early and late events in T-cell receptor-mediated T-cell activation. Moreover, we found that CAPE specifically inhibited both interleukin (IL)-2 gene transcription and IL-2 synthesis in stimulated T-cells. To further characterize the inhibitory mechanisms of CAPE at the transcriptional level, we examined the DNA binding and transcriptional activities of nuclear factor (NF)-kappaB, nuclear factor of activated cells (NFAT), and activator protein-1 (AP-1) transcription factors in Jurkat cells. We found that CAPE inhibited NF-kappaB-dependent transcriptional activity without affecting the degradation of the cytoplasmic NF-kappaB inhibitory protein, IkappaBalpha. However, both NF-kappaB binding to DNA and transcriptional activity of a Gal4-p65 hybrid protein were clearly prevented in CAPE-treated Jurkat cells. Moreover, CAPE inhibited both the DNA-binding and transcriptional activity of NFAT, a result that correlated with its ability to inhibit phorbol 12-myristate 13-acetate plus ionomycin-induced NFAT1 dephosphorylation. These findings provide new insights into the molecular mechanisms involved in the immunomodulatory and anti-inflammatory activities of this natural compound.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caffeic Acids / pharmacology*
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • DNA-Binding Proteins / metabolism
  • Humans
  • Interleukin-2 / metabolism
  • Jurkat Cells
  • Lymphocyte Activation / drug effects*
  • NF-kappa B / metabolism*
  • NFATC Transcription Factors
  • Nuclear Proteins*
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / pharmacology*
  • Phosphorylation / drug effects
  • Promoter Regions, Genetic / drug effects
  • T-Lymphocytes / drug effects*
  • T-Lymphocytes / metabolism
  • Transcription Factors / metabolism
  • Transcriptional Activation / drug effects


  • Caffeic Acids
  • DNA-Binding Proteins
  • Interleukin-2
  • NF-kappa B
  • NFATC Transcription Factors
  • NFATC2 protein, human
  • Nuclear Proteins
  • Transcription Factors
  • caffeic acid phenethyl ester
  • Phenylethyl Alcohol