Invited Symposium: Medicinal Plants and Drug Actions
Chang, DM (Rheumatology/Immunology and Allergy, Tri-Service General Hospital, Taiwan ROC)
Lee, DT (Army 802 Hospital, Taiwan ROC)
Chang, ML (Rheumatology/Immunology and Allergy, Tri-Service General Hospital, Taiwan ROC)
Lai, JH (Rheumatology/Immunology and Allergy, Tri-Service General Hospital, Taiwan ROC)
Tetrandrine, a purified traditional chinese medicinal herb functioning as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients of arthritis, silicosis and hypertension. Since T cells play a critical role as autoreactive and pathogenic population in autoimmune diseases, in this study, we examined the immunosuppressive effect of tetrandrine in human peripheral blood T cells. We showed that tetrandrine inhibited phorbol 12-myristate 13-acetate (PMA)+ionomycin-induced T cell proliferation, interleukin-2 secretion and the expression of T cell activation antigen, CD71. Further dissection of the molecular mechanism demonstrated that tetrandrine inhibited protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 expression but not the Ca2+-dependent CD40 ligand and CD69 expression. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in suppression of T cell activation was observed. Moreover, of the several tetrandrine analogues studied, hernandezine was the most potent inhibitor of protein kinase C signaling events. These results also suggest that the protein kinase C-inhibitory capacity of tetrandrine and its analogues may not be associated with their function as Ca2+ channel blockers. Lastly, we showed that, within therapeutic concentration, tetrandrine and its analogues could induce cellular apoptosis which is defective in autoimmune diseases. In conclusion, our findings provide novel information about the molecular mechanism of the immunosuppressive effect of tetrandrine and its analogues in human peripheral blood T cells.
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|Ho, LJ; Chang, DM; Lee, DT; Chang, ML; Lai, JH; (1998). Plant Alkaloid Tetrandrine and Its Analogues Downregulates Protein Kinase C dependent but not Ca2+-dependent Signaling Pathway in Human Peripheral Blood T Cells. Presented at INABIS '98 - 5th Internet World Congress on Biomedical Sciences at McMaster University, Canada, Dec 7-16th. Invited Symposium. Available at URL http://www.mcmaster.ca/inabis98/kwan/ho0415/index.html|
|© 1998 Author(s) Hold Copyright|