The effect of rapamycin on c-jun expression in human lymphocytes.

Rapamycin (RAPA) is a potent immunosuppressant. Several reports indicate that the drug can act at the late G1 stage of the lymphocyte activation. We studied the effect of RAPA on the expression of an immediate early phase gene c-jun, which plays a pivotal role in cell activation. The results showed that RAPA could inhibit PHA-induced c-jun expression by human T cells. This strongly suggests that there exists a mechanism for RAPA to interact with the lymphocyte activation cascade at a very early stage. We also demonstrated that in T cells a Na+/K+ ATPase inhibitor, ouabain, could induce a late (16 h poststimulation) c-jun expression, which was sensitive to cyclosporin A (CsA) but not to RAPA. This suggests that c-jun's role is probably not restricted to the early phase of lymphocyte activation.