Cyclic AMP- and IL6-Signaling Cross Talk: Comodulation of Proliferation and Apoptosis in the 7TD1 B Cell Hybridoma

Abstract

Proliferation of the 7TD1 B cell hybridoma is dependent on the survival factor interleukin-6 (IL6). IL6 inhibits physiological cell death and allows expansion of populations of serum-stimulated cells. In this report, we demonstrate that cyclic AMP (cAMP)- and IL6-dependent signaling pathways can interact, controlling proliferation of 7TD1 cells through modulation of apoptosis. Cyclic AMP analogues inhibited proliferation, as well as other treatments that increased intracellular cAMP. The cAMP-induced inhibition could be reversed after 24 h by the removal of dibutyryl-cAMP from the culture medium and readdition of IL6. In the absence of IL6, cAMP induced a slow loss of viable cells. This decrease in viable cells in the presence of cAMP was accompanied by a marked increase in apoptosis. The increase in apoptotic cells after 48 h was preceded at 24 h by a parallel increase in DEVD-caspase activity after treatment with cell-permeable cAMP analogues. Increased DEVD-caspase activity and subsequent apoptosis could both be blocked by the addition of IL6. These coregulating actions may represent a cross-talk signaling mechanism modulating cytokine activation of cellular proliferation and survival.