Saikosaponin-d inhibits T cell activation through the modulation of PKCtheta, JNK, and NF-kappaB transcription factor

Abstract

The effects of saikosaponin-d, a triterpene saponin derived from Bupleurum falcatum L. (Umbelliferae), on the signaling pathways of T cell activation were examined. The results showed that saikosaponin-d potently suppressed both early (CD69) and late (CD71) expressions of mouse T cells stimulated with Con A or PMA. It interfered with PKCtheta translocation from cytosol to membrane fraction and inhibited the phosphorylations of IkappaBalpha and JNK, but not ERK, in PMA-activated mouse T cells. Additionally, it inhibited PMA and ionomycin-stimulated IL-2 production in mouse T cells. In summary, these results indicate that the mechanism by which saikosaponin-d inhibits T cell activation would involve the suppression of CD69 and CD71 expressions and IL-2 production, and the modulation of PKC pathway through PKCtheta, JNK, and NF-kappaB transcription factor. This may herald a novel approach for further studies of saikosaponin-d as a candidate for use in the treatment of inflammatory and autoimmune diseases.