Interleukin-1β Induced Synthesis of Protein Kinase C-δ and Protein Kinase C-ε in EL4 Thymoma Cells: Possible Involvement of Phosphatidylinositol 3-Kinase

We present evidence here that the proinflammatory cytokine, interleukin-1β (IL-1β) stimulates a significant increase in protein kinase C (PKC)-Ε and PKC-δ protein levels and increases PKC-Ε, but not PKC-δ, transcripts in EL4 thymoma cells. Incubation of EL4 cells with IL-1β induced protein synthesis of PKC-Ε (6-fold increase) by 7 h and had a biphasic effect on PKC-δ levels with peaks at 4 h (2-fold increase) and 24 h (4-fold increase). At the level of mRNA, PKC-Ε, but not PKC-δ levels, were induced after incubation of EL4 cells with IL-1β. The signalling mechanisms utilized by IL-1β to induce the synthesis of these PKC isoforms were investigated. Two phosphatidylinositol (PI) 3-kinase-specific inhibitors, wortmannin and LY294002, inhibited IL-1β-induced synthesis of PKC-Ε. However, the PI 3-kinase inhibitors had little effect on the IL-1β-induced synthesis of PKC-δ in these cells. Our results indicate that IL-1β induced both PKC-δ and PKC-Ε expression over different time periods. Furthermore, our evidence suggests that IL-1β induction of PKC-Ε, but not PKC-δ, may occur via the PI 3-kinase pathway.