Saikosaponin-d inhibits T cell activation through the modulation of PKCtheta, JNK, and NF-kappaB transcription factor.
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.
Leung
Chung Yee
CY
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong.
Liu
Liang
L
Wong
Ricky N S
RN
Zeng
Yao Ying
YY
Li
Ming
M
Zhou
Hua
H
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D020672:I-kappa B Proteins / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007527:Isoenzymes / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology*; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000502:physiology*; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology*; D000074121:Protein Kinase C-theta; D011990:Receptors, Transferrin / Q000096:biosynthesis; D012503:Saponins / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects*; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D048049:Extracellular Signal-Regulated MAP Kinases; D020672:I-kappa B Proteins; D007376:Interleukin-2; D007527:Isoenzymes; D048031:JNK Mitogen-Activated Protein Kinases; D037181:Lectins, C-Type; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B; D009828:Oleanolic Acid; D011493:Protein Kinase C; D000074121:Protein Kinase C-theta; D011990:Receptors, Transferrin; D012503:Saponins; D000099192:CD69 Antigens; C068126:CD71 antigen; C000606205:Nfkbia protein, mouse; C489593:Prkcq protein, mouse; C025759:saikosaponin D