Cyclic AMP- and IL6-signaling cross talk: Comodulation of proliferation and apoptosis in the 7TD1 B cell hybridoma

Proliferation of the 7TD1 B cell hybridoma is dependent on the survival fac tor interleukin-g (IL6). IL6 inhibits physiological cell death and allows e xpansion of populations of serum-stimulated cells. In this report, we demon strate that cyclic AMP (cAMP)- and IL6-dependent signaling pathways can int eract, controlling proliferation of 7TD1 cells through modulation of apopto sis, Cyclic AMP analogues inhibited proliferation, as well as other treatme nts that increased intracellular cAMP. The cAMP-induced inhibition could be reversed after 24 h by the removal of dibutyryl-cAMP from the culture medi um and readdition of IL6. In the absence of IL6, cAMP induced a slow loss o f viable cells. This decrease in viable cells in the presence of cAMP was a ccompanied by a marked increase in apoptosis, The increase in apoptotic cel ls after 48 h was preceded at 24 h by a parallel increase in DEVD-caspase a ctivity after treatment with cell-permeable cAMP analogues. Increased DEVD- caspase activity and subsequent apoptosis could both be blocked by the addi tion of IL6. These coregulating actions may represent a cross-talk signalin g mechanism modulating cytokine activation of cellular proliferation and su rvival. (C) 2001 Academic Press.