Activation of cellular responses to interleukin 6 is blocked by staurosporine.
Interleukin 6 (IL-6) acts on a wide spectrum of cells and can regulate differentiation or growth in these different cells. The effects of the microbial alkaloid staurosporine (SS) on IL-6 signaling through gp130, and also on the internalization of the IL-6 receptor complex, were studied using HepG2 cells which are well-characterized in their ability to respond to IL-6 by upregulating acute-phase protein production. SS was found effective in the blockade of the signaling cascade of IL-6: phosphorylation of both gp130 and Stat3 was eliminated by SS treatment and the production of IL-6 stimulated haptoglobin by the cells was abolished. In addition, SS reduced the internalization rate of 125I-IL-6 by 50%, resulting in a retention of 125I-IL-6 on the cell surface and a corresponding decrease in degraded 125I-IL-6 in the extracellular medium. SS is commonly employed as an apoptosis inducing agent but the mechanism of its action is not clear. The ability of SS to void the capacity of IL-6, and IL-6-related cytokines such as Oncostatin M, to deliver growth and differentiation signals may be one process by which this agent could promote apoptosis in a variety of cell types.
Peppard
J V
JV
Core Technologies, Novartis Institute for Biomedical Research, Summit, NJ 07901, USA. jane.peppard@pharma.novartis.com
D004268:DNA-Binding Proteins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D006242:Haptoglobins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D009025:Morpholines / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000187:drug effects*; D019311:Staurosporine / Q000378:metabolism / Q000494:pharmacology*; D015534:Trans-Activators / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D006242:Haptoglobins; D015850:Interleukin-6; D009025:Morpholines; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D015534:Trans-Activators; C005759:2-phenyl-5,5-dimethyltetrahydro-1,4-oxazine; D019311:Staurosporine