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 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.
Department of Pharmaceutical Sciences, Idaho State University, Pocatello, Idaho 83209, USA.
B J
BJ
Irvin
C L
CL
Hanson
L H
LH
Smith
C K
CK
Daniels
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D003994:Bucladesine / Q000378:metabolism / Q000494:pharmacology; D020169:Caspases / Q000378:metabolism; D002455:Cell Division; D003374:Coumarins / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D006825:Hybridomas; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology; D015398:Signal Transduction
D003374:Coumarins; D015850:Interleukin-6; D009842:Oligopeptides; C115495:aspartyl-glutamyl-valyl-aspartyl-7-amino-4-trifluoromethylcoumarin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D003994:Bucladesine; D000242:Cyclic AMP; D020169:Caspases