Abstract
It is known that during acute phase reaction IL-6 activates STAT3 in hepatoma cells and IL-1 downregulates this response. We found that the inhibitory properties of IL-1 on STAT signalling cascade in human hepatoma HepG2 cells are considerably decreased not only in the presence of MAP kinase inhibitors SB203580 and PD98059 but also by some antioxidants (N-acetyl cysteine and pyrrolidine dithiocarbamate) and by anti-inflammatory cytokine IL-4. It appears that cytokine crosstalk between IL-6 and IL-1 includes a direct pathway sensitive to antioxidants and MAP kinase inhibitors, whereas the indirect prolonged response depends probably on synthesis of suppressors of cytokine signalling (SOCS).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Anti-Inflammatory Agents / pharmacology
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Antioxidants / classification
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Antioxidants / metabolism
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Antioxidants / pharmacology
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Cells, Cultured
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DNA-Binding Proteins / agonists
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / metabolism*
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Enzyme Inhibitors / pharmacology
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Flavonoids / pharmacology
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Humans
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Imidazoles / pharmacology
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Interleukin-1 / antagonists & inhibitors
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Interleukin-1 / metabolism
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Interleukin-1 / pharmacology*
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Interleukin-4 / metabolism
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Interleukin-4 / pharmacology*
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Interleukin-6 / antagonists & inhibitors*
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Interleukin-6 / metabolism
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Interleukin-6 / pharmacology
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Mitogen-Activated Protein Kinases / antagonists & inhibitors*
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Oxidation-Reduction
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Pyridines / pharmacology
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Receptor Cross-Talk
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STAT3 Transcription Factor
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Signal Transduction
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Trans-Activators / agonists
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Trans-Activators / biosynthesis
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Trans-Activators / metabolism*
Substances
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Anti-Inflammatory Agents
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Antioxidants
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DNA-Binding Proteins
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Enzyme Inhibitors
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Flavonoids
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Imidazoles
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Interleukin-1
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Interleukin-6
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Pyridines
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STAT3 Transcription Factor
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STAT3 protein, human
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Trans-Activators
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Interleukin-4
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Mitogen-Activated Protein Kinases
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SB 203580
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one