Dissociated Control by Glycyrrhizin of Proliferation and IL-2 Production of Murine Thymocytes

The action of glycyrrhizin (GL) modulating the proliferation and IL-2 production of murine thymocytes in response to anti-CD3 and concanavalin A was studied. Different from the previously reported GL effect of accelerating both IL-2 production and proliferation of mature T lymphocytes, GL displayed a dissociated action on immature thymocytes promoting IL-2 production/IL-2 receptor expression but inhibiting cell growth. Hydrocortisone-resistant mature thymocytes behaved like peripheral T lymphocytes, demonstrating the dependency of the GL action on cell maturation stage. GL-mediated growth inhibition of thymocytes was not due the cytotoxic action of GL that induces cell death or DNA fragmentation. In parallel to these dissociated actions, GL promoted the tyrosine phosphorylation of p56 but suppressed the phosphorylation of p40 induced by anti-CD3. Moreover, GL and anti-CD3 showed a combination effect suppressing the transcription of c-fos, which was promoted by anti-CD3 alone or GL alone. It is suggested that whereas mature and immature T cells share a common signal pathway for IL-2 production augmented by the action of GL, they have signaling steps for DNA synthesis which are under different mechanisms receiving the modulation effects of GL in opposite directions.