CHARACTERIZATION OF THE IMMUNOREGULATORY ACTION OF SAIKOSAPONIN-D

The immunoregulatory action of saikosaponin-d (SSd), which was isolate d from the root of Bupleurum falcatum L. and has a steroid-like struct ure, was examined on splenic T lymphocytes of C57BL/6 mice. SSd displa yed a definite action in vitro to bidirectionally control the growth r esponse of T lymphocytes stimulated by concanavalin A, anti-CD3 monocl onal antibody, and calcium ionophore A23187 plus phorbol 12-myristate 13-acetate. Low concentrations (1-3 mu g/ml) of SSd upregulated the re sponses to suboptimum stimuli of agonists, particularly during the rel atively late stage of the responses, whereas it downregulated the resp onses to supraoptimal stimuli. Under appropriate experimental conditio ns, SSd promoted interleukin-2 (IL-2) production and IL-2 receptor exp ression. It also accelerated c-fos gene transcription, but it did not modulate the level of tyrosine phosphorylation of cellular proteins. W e concluded from these results that SSd uniquely modulates T lymphocyt e function and that at least one target of the action of SSd is locate d at or before the step of c-fos gene transcription and after T-cell r eceptor/CD3-mediated protein tyrosine kinase activation. (C) 1994 Acad emic Press, Inc.