IL-1-mediated inhibition of IL-6-induced STAT3 activation is modulated by IL-4, MAP kinase inhibitors and redox state of HepG2 cells.
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).
Cisowski
Jarosław
J
Department of Cellular Biochemistry, Institute of Molecular Biology and Biotechnology, Jagiellonian University, Kraków, Poland.
Zarebski
Adrian
A
Koj
Aleksander
A
D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000145:classification / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D015847:Interleukin-4 / Q000378:metabolism / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D011725:Pyridines / Q000494:pharmacology; D020239:Receptor Cross-Talk; D050796:STAT3 Transcription Factor; D015398:Signal Transduction; D015534:Trans-Activators / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D000093242:Interleukin-6 Inhibitors
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D007375:Interleukin-1; D015847:Interleukin-4; D015850:Interleukin-6; D020928:Mitogen-Activated Protein Kinases; D011725:Pyridines; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D000093242:Interleukin-6 Inhibitors; C494086:STAT3 protein, human; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one