Involvement of protein kinases in staurosporine-induced chemokine production by rat peritoneal neutrophils

When rat peritoneal neutrophils were incubated for 4 h in medium containing staurosporine (SS, 6.4-64 nM), the neutrophil chemotactic activity in the conditioned medium increased in a concentration-dependent manner. The increase of neutrophil chemotactic activity in the conditioned medium by SS was mainly due to the increase of cytokine-induced neutrophil chemoattractant (CINC)-3 production. TPA (49 nM) also induced CINC-3 production. The SS-induced neutrophil chemotactic factor production was inhibited by the protein kinase C (PKC) inhibitors H-7 (8.2-82 μM), calphostin C (1 and 3 μM) and Ro 31-8425 (10 μM), and by the tyrosine kinase inhibitor genistein (37-185 μM). The TPA-induced neutrophil chemotactic factor production was also inhibited by both inhibitors. RT-PCR analysis demonstrated that both the SS- and the TPA-induced accumulation of CINC-3 mRNA at 2 h were also decreased by H-7 and genistein. These findings suggest that the SS-induced CINC-3 production involves the activities of PKC and tyrosine kinase.