Acetaminophen down-regulates interleukin-1β-induced nuclear factor-κB nuclear translocation in a human astrocytic cell line

Francesca Mancini, Carla Landolfi, Marta Muzio, Luciano Aquilini, Lucia Soldo, Isabella Coletta, Angelo Guglielmotti, Alberto Mantovani, Mario Pinza, Claudio Milanese

Research output: Contribution to journalArticlepeer-review

Abstract

In previous studies performed to elucidate acetaminophen mechanism of action, we demonstrated that acetaminophen inhibits prostaglandin E2 production by interleukin (IL)-1β-stimulated T98G human astrocytic cells, without affecting cyclooxygenase-2 enzymatic activity. As this result suggests an effect at transcriptional level, we examined whether the drug interferes with the activation of nuclear factor (NF)-κB and STAT3 transcription factors and with SAPK signal transducing factor. Western blot analysis of IκBα protein in the cytoplasm of IL-1β-stimulated T98G cells and electrophoretic mobility shift assay (EMSA) on corresponding nuclear extracts indicate that acetaminophen (10-1000 μM) dose-dependently inhibits both IκBα degradation and NF-κB nuclear translocation. In the same cell type neither IL-1β-dependent SAPK activation nor IL-6-induced STAT3 phosphorylation is affected by the drug. These data indicate that therapeutic concentrations of acetaminophen induce an inhibition of IL-1β-dependent NF-κB nuclear translocation. The selectivity of this effect suggests the existence of an acetaminophen specific activity at transcriptional level that may be one of the mechanisms through which the drug exerts its pharmacological effects.

Original languageEnglish
Pages (from-to)79-82
Number of pages4
JournalNeuroscience Letters
Volume353
Issue number2
DOIs
Publication statusPublished - Dec 19 2003

Keywords

  • Acetaminophen
  • Interleukin-1β
  • NF-κB
  • Nuclear translocation
  • Signal transcription
  • Signal transduction

ASJC Scopus subject areas

  • Neuroscience(all)

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