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 language | English |
|---|---|
| Pages (from-to) | 79-82 |
| Number of pages | 4 |
| Journal | Neuroscience Letters |
| Volume | 353 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Dec 19 2003 |
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Keywords
- Acetaminophen
- Interleukin-1β
- NF-κB
- Nuclear translocation
- Signal transcription
- Signal transduction
ASJC Scopus subject areas
- Neuroscience(all)
Cite this
Acetaminophen down-regulates interleukin-1β-induced nuclear factor-κB nuclear translocation in a human astrocytic cell line. / Mancini, Francesca; Landolfi, Carla; Muzio, Marta; Aquilini, Luciano; Soldo, Lucia; Coletta, Isabella; Guglielmotti, Angelo; Mantovani, Alberto; Pinza, Mario; Milanese, Claudio.
In: Neuroscience Letters, Vol. 353, No. 2, 19.12.2003, p. 79-82.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Acetaminophen down-regulates interleukin-1β-induced nuclear factor-κB nuclear translocation in a human astrocytic cell line
AU - Mancini, Francesca
AU - Landolfi, Carla
AU - Muzio, Marta
AU - Aquilini, Luciano
AU - Soldo, Lucia
AU - Coletta, Isabella
AU - Guglielmotti, Angelo
AU - Mantovani, Alberto
AU - Pinza, Mario
AU - Milanese, Claudio
PY - 2003/12/19
Y1 - 2003/12/19
N2 - 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.
AB - 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.
KW - Acetaminophen
KW - Interleukin-1β
KW - NF-κB
KW - Nuclear translocation
KW - Signal transcription
KW - Signal transduction
UR - http://www.scopus.com/inward/record.url?scp=10744231277&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744231277&partnerID=8YFLogxK
U2 - 10.1016/j.neulet.2003.08.074
DO - 10.1016/j.neulet.2003.08.074
M3 - Article
C2 - 14664905
AN - SCOPUS:10744231277
VL - 353
SP - 79
EP - 82
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 2
ER -