N-Acetylcysteine suppresses TNF-induced NF-κB activation through inhibition of IκB kinases

Shin Ichi Oka, Hideaki Kamata, Keiko Kamata, Hitoshi Yagisawa, Hajime Hirata

Research output: Contribution to journalArticlepeer-review

126 Scopus citations


Here, we used a reductant, N-acetyl-L-cysteine (NAC), to investigate the redox-sensitive step(s) in the signalling pathway from the tumor necrosis factor (TNF) receptor to nuclear factor κB (NF-κB). We found that NAC suppressed NF-κB activation triggered by TNF or by overexpression of either the TNF receptor-associated death domain protein, TNF receptor-associated factor 2, NF-κB-inducing kinase (NIK), or IκB kinases (IKKα and IKKβ). NAC also suppressed the TNF-induced activation of IKKα and IKKβ, phosphorylation and degradation of IκB, and nuclear translocation of NF-κB. Furthermore, NAC suppressed the activation of IKKα and IKKβ triggered by the overexpression of NIK. These results indicate that IKKα and IKKβ are subject to redox regulation in the cells, and that NAC inhibits NF-κB activation through the suppression of these kinases.

Original languageAmerican English
Pages (from-to)196-202
Number of pages7
JournalFEBS Letters
Issue number2-3
StatePublished - Apr 28 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


  • IκB kinase
  • N-Acetyl-L-cysteine
  • Nuclear factor κB
  • Redox
  • Tumor necrosis factor


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