LPS and TNFalpha induce SOCS3 mRNA and inhibit IL-6-induced activation of STAT3 in macrophages.
Recent findings indicate that cytokine signaling can be modulated by other mediators of simultaneously activated signal transduction pathways. In this study we show that LPS and TNFalpha are potent inhibitors of IL-6-mediated STAT3 activation in human monocyte derived macrophages, rat liver macrophages and RAW 264.7 mouse macrophages but not in human hepatoma cells (HepG2) or in rat hepatocytes. Accordingly, LPS and TNFalpha were found to induce the expression of SOCS3 mRNA in each of the investigated type of macrophages but not in HepG2 cells. Using a specific inhibitor, evidence is presented that the p38 MAP kinase might be involved, especially for the inhibitory effect of TNFalpha.
Bode
J G
JG
Institut für Biochemie, Klinikum der RWTH Aachen, Pauwelsstrasse 30, 52057, Aachen, Germany.
Nimmesgern
A
A
Schmitz
J
J
Schaper
F
F
Schmitt
M
M
Frisch
W
W
Häussinger
D
D
Heinrich
P C
PC
Graeve
L
L
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D016153:Genes, Suppressor; D006801:Humans; D007728:Kupffer Cells / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D015534:Trans-Activators / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors
D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D020928:Mitogen-Activated Protein Kinases; D050796:STAT3 Transcription Factor; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D000093242:Interleukin-6 Inhibitors; C494086:STAT3 protein, human; C494087:Stat3 protein, mouse; C494088:Stat3 protein, rat