Staurosporine, but not Ro 31-8220, induces interleukin 2 production and synergizes with interleukin 1α in EL4 thymoma cells: Activation of nuclear factor κB as a common signal for staurosporine and interleukin 1α

Abstract

Protein kinase C (PKC) has been implicated in interleukin 1 (IL1) signal transduction in a number of cellular systems, either as a key event in IL1 action or as a negative regulator. Here we have examined the effects of two PKC inhibitors, staurosporine and the more selective agent Ro 31-8220, on IL1 responses in the murine thymoma line EL4.NOB-1. A 1 h pulse of staurosporine was found to strongly potentiate the induction of IL2 by IL1α in these cells. In contrast, neither a pulse nor prolonged incubation with Ro 31-8220 affected the response to IL1α. Both agents blocked the response to PMA, however. A 1 h pulse of staurosporine was also found to induce IL2 production on its own, activate the transcription factor nuclear factor κB (NFκB) and increase the expression of a NFκB-linked reporter gene. It synergized with IL1α in all of these responses. Ro 31-8220 was again without effect, although both staurosporine and Ro 31-8220 blocked the activation of NFκB by PMA. Finally, staurosporine caused the translocation of PKC-α and -ϵ, and to a lesser extent PKC-β, but not PKC-θ or -ζ, from the cytosol to the membrane, although a similar effect was observed with Ro 31-8220. The results suggest that PKC is not involved in IL1α signalling in EL4 cells. Furthermore, the potentiating effect of staurosporine on IL1α action does not involve PKC inhibition, and is likely to be at the level of NFκB activation.