Effects of anti-proliferative cyclic AMP on interleukin 2-stimulated gene expression.

Elevation of intracellular cyclic adenosine 3':5' monophosphate (cAMP) inhibits interleukin 2 (IL-2)-stimulated proliferation of a murine cytotoxic cell clone, CT6. The effects of antiproliferative dosages of stable cAMP-derivative, 8-bromoadenosine 3':5'-monophosphate (8-Br-cAMP), on steady state mRNA expression stimulated by IL-2 was examined. IL-2 stimulated mRNA accumulation of three nuclear proto-oncogenes c-fos, c-myc, and c-myb. 8-Br-cAMP alone stimulated c-fos, c-myb, and IL-2 receptor mRNA accumulation as determined by Northern blot analysis. 8-Br-cAMP, however, markedly inhibited c-myc expression stimulated by IL-2. Furthermore, although c-fos and IL-2 receptor mRNA expression was potentiated by 8-Br-cAMP, suppression of protein synthesis was seen. We show that antiproliferative cAMP stimulates similar mRNA expression as does IL-2, with the exception of c-myc. Although a comparative stimulation of steady state mRNA accumulation of some genes occurs, cAMP may profoundly effect protein synthesis. cAMP, therefore, acts on multiple targets involved in the macromolecular events stimulated by IL-2.