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

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Abstract

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
Volume268
Issue number24
DOIs
Publication statusPublished - 2001 Dec 1

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Keywords

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

ASJC Scopus subject areas

  • Biochemistry

Cite this

Tago, K., Funakoshi, M., Mano, H., Yanagisawa, K., Hayakawa, M., Kuroiwa, K., Iwahana, H., Kasahara, T., & Tominaga, S. I. (2001). Presence of a genistein-responsive inhibitory mechanism on interleukin-1αa-induced NF-κkB activation. European Journal of Biochemistry, 268(24), 6526-6533. https://doi.org/10.1046/j.1432-1327.2001.02603.x