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- W1974520908 abstract "The incubation of rat peritoneal macrophages in the presence of staurosporine, a non-specific protein kinase inhibitor, induced interleukin-6 (IL-6) production in a time- and concentration-dependent manner at 6.3–63 nM, but at 210 nM, the stimulant effect on IL-6 production was reduced. The levels of IL-6 mRNA as determined by a reverse transcription-polymerase chain reaction were also increased by staurosporine in parallel with the ability to induce IL-6 production. Compounds structurally related to staurosporine including K-252a (non-specific protein kinase inhibitor) and KT-5720 (inhibitor of cyclic AMP-dependent protein kinase, PKA), did not increase IL-6 production by peritoneal macrophages. Staurosporine-induced increases in IL-6 production and expression of IL-6 mRNA were decreased by the PKC inhibitors, H-7 (2.7–27 μM), Ro 31–8425 (1–10 μM) and calphostin C (0.3–3 μM) and by the phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor LY294002 (30–100 μM), but were further increased by the protein tyrosine kinase (PTK) inhibitor, genistein (12–37 μM). The staurosporine-induced increase in IL-6 production was not affected by the PKA inhibitor, H-89 (0.1–3 μM). These findings suggest that the induction of IL-6 production by staurosporine is secondary to elevation of IL-6 mRNA level, which, in turn, is positively regulated by the activation of PKC and PI 3-kinase and negatively regulated by the activation of PTK. PKA does not appear to play a significant role. British Journal of Pharmacology (1999) 127, 1309–1316; doi:10.1038/sj.bjp.0702659" @default.
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- W1974520908 date "1999-07-01" @default.
- W1974520908 modified "2023-10-18" @default.
- W1974520908 title "Participation of protein kinases in staurosporine-induced interleukin-6 production by rat peritoneal macrophages" @default.
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- W1974520908 doi "https://doi.org/10.1038/sj.bjp.0702659" @default.
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