Activation of interleukin-2 receptor gene by forskolin and cyclic AMP analogues.

Forskolin (FK), a reversible activator of adenylate cyclase, markedly enhanced the expression of interleukin-2 receptor (IL-2-R) on a human natural killer (NK)-like cell line, YT. The FK-induced increase in IL-2-R on YT cells closely correlated with an increase in intracellular cyclic AMP (cAMP) level, and was mimicked by dibutyryl cyclic AMP (dbcAMP). FK induced both high and low affinity IL-2-R on the cells. Using a cDNA for the IL-2-R as a probe, the FK-induced IL-2-R expression was shown to be associated with an increase in IL-2-R mRNA. FK also enhanced the IL-2-R expression on a human T lymphotrophic virus I (HTLV-I) positive T-cell line (YTA-1H) and augmented the phorbol ester-induced expression of IL-2-R on HTLV-I negative T-cell lines (HSB-2 and HPB-ALL). These results suggest the possibility that the stimulation of adenylate cyclase may serve as a pathway leading to activation of the IL-2-R gene in certain types of lymphocytes.