Presence of a genistein-responsive inhibitory mechanism on interleukin-1αa-induced NF-κkB activation

Kenji Tago, Megumi Funakoshi, Hiroyuki Mano, Ken Yanagisawa, Morisada Hayakawa, Kenji Kuroiwa, Hiroyuki Iwahana, Tadashi Kasahara, Shin Ichi Tominaga

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


Interleukin 1 (IL-1) is known to activate the signal transduction machinery, including the transcription factor, nuclear factor kappa B (NF-κB). The activation mechanism of NF-κB has been studied intensively, while the negative regulatory mechanisms of NF-κB remain to be clarified. In the present study, we found that genistein, a tyrosine kinase inhibitor, augmented IL-1α-dependent NF-κB activation, suggesting the presence of a tyrosine kinase mediating a suppression signal on NF-κB. As determined by luciferase reporter gene assay using κB-responsive element, genistein enhanced IL-1α-induced NF-κB activation. Although genistein failed to increase luciferase activity at 1 and 3 h after IL-1α stimulation, it induced prolonged activation beginning at 6 h after the initial stimulation. We next examined whether genistein augmented the DNA-binding activity of NF-κB, using electrophoretic mobility shift assay. In the case of the control experiment, the binding of NF- κB to the κB-responsive element peaked at 30 min after IL-1α stimulation, and decreased thereafter. In contrast, treatment with genistein maintained the maximum binding activity for at least 2 h after stimulation. Moreover, genistein enhanced the IL-1α-dependent degradation of IκBa. Taken together, our results indicate that genistein augments IκkB degradation, resulting in continuous NF-κB activation. This suggests the possibility that tyrosine kinase negatively regulates NF-κB.

Original languageEnglish
Pages (from-to)6526-6533
Number of pages8
JournalEuropean Journal of Biochemistry
Issue number24
Publication statusPublished - 2001


  • Genistein
  • Interleukin-1
  • IκBα
  • Nuclear factor κB

ASJC Scopus subject areas

  • Biochemistry


Dive into the research topics of 'Presence of a genistein-responsive inhibitory mechanism on interleukin-1αa-induced NF-κkB activation'. Together they form a unique fingerprint.

Cite this