Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells
Identifieur interne : 002603 ( Main/Exploration ); précédent : 002602; suivant : 002604Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells
Auteurs : Ling-Jun Ho [République populaire de Chine] ; Deh-Ming Chang [République populaire de Chine] ; Ta-Chung Lee [République populaire de Chine] ; Mu-Lan Chang [République populaire de Chine] ; Jenn-Haung Lai [République populaire de Chine]Source :
- European Journal of Pharmacology [ 0014-2999 ] ; 1999.
English descriptors
- Teeft :
- Alkaloid, Alveolar macrophages, Analogue, Apoptosis, Arthritis rheum, Assay, Autoimmune, Autoimmune diseases, Berbamine, Ca2q, Ca2q channel, Ca2q channel blocker, Cell activation, Cell proliferation, Cell receptor, Chain expression, Chang, Cyclosporin, Different donors, European journal, Flow cytometry, Fluorescence intensity, Hernandezine, Immunol, Immunosuppressive, Immunosuppressive activity, Immunosuppressive effect, Immunosuppressive effects, Inhibitory effect, Inhibitory effects, Ionomycin, Kinase, Kwan, Leung, Ligand, Lymphocyte, Macrophage, Mast cells, Monoclonal antibody, National defense, Ngrmlq ionomycin, Pathway, Peripheral blood, Pharmacol, Pharmacology, Protein kinase, Protein kinase effect, Receptor, Room temperature, Tetrandrine, Therapeutic effect, Thong, Various concentrations, Various times.
Abstract
Abstract: Tetrandrine, a purified traditional Chinese medicinal herb that acts as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients with 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 on 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 the T cell activation antigen, CD71. Further investigation of the molecular mechanism demonstrated that tetrandrine inhibited the expression of the protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in the 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 concentrations, 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.
Url:
DOI: 10.1016/S0014-2999(98)00941-8
Affiliations:
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cells</title><author><name sortKey="Ho, Ling Jun" sort="Ho, Ling Jun" uniqKey="Ho L" first="Ling-Jun" last="Ho">Ling-Jun Ho</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan</wicri:regionArea><wicri:noRegion>Taiwan</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Deh Ming" sort="Chang, Deh Ming" uniqKey="Chang D" first="Deh-Ming" last="Chang">Deh-Ming Chang</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Rheumatology/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 8, Sec. 3, Ting-Chow Rd., Taipei, Taiwan</wicri:regionArea><wicri:noRegion>Taiwan</wicri:noRegion></affiliation></author><author><name sortKey="Lee, Ta Chung" sort="Lee, Ta Chung" uniqKey="Lee T" first="Ta-Chung" last="Lee">Ta-Chung Lee</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Army 802 Hospital, Kaoshung, Taiwan</wicri:regionArea><wicri:noRegion>Taiwan</wicri:noRegion></affiliation></author><author><name sortKey="Chang, Mu Lan" sort="Chang, Mu Lan" uniqKey="Chang M" first="Mu-Lan" last="Chang">Mu-Lan Chang</name><affiliation wicri:level="1"><country xml:lang="fr" wicri:curation="lc">République populaire de Chine</country><wicri:regionArea>Rheumatology/Immunology and Allergy, Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 8, Sec. 3, Ting-Chow Rd., Taipei, Taiwan</wicri:regionArea><wicri:noRegion>Taiwan</wicri:noRegion></affiliation></author><author><name sortKey="Lai, Jenn Haung" sort="Lai, Jenn Haung" uniqKey="Lai J" first="Jenn-Haung" last="Lai">Jenn-Haung Lai</name><affiliation wicri:level="1"><country xml:lang="fr" 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xml:lang="en"><term>Alkaloid</term><term>Alveolar macrophages</term><term>Analogue</term><term>Apoptosis</term><term>Arthritis rheum</term><term>Assay</term><term>Autoimmune</term><term>Autoimmune diseases</term><term>Berbamine</term><term>Ca2q</term><term>Ca2q channel</term><term>Ca2q channel blocker</term><term>Cell activation</term><term>Cell proliferation</term><term>Cell receptor</term><term>Chain expression</term><term>Chang</term><term>Cyclosporin</term><term>Different donors</term><term>European journal</term><term>Flow cytometry</term><term>Fluorescence intensity</term><term>Hernandezine</term><term>Immunol</term><term>Immunosuppressive</term><term>Immunosuppressive activity</term><term>Immunosuppressive effect</term><term>Immunosuppressive effects</term><term>Inhibitory effect</term><term>Inhibitory effects</term><term>Ionomycin</term><term>Kinase</term><term>Kwan</term><term>Leung</term><term>Ligand</term><term>Lymphocyte</term><term>Macrophage</term><term>Mast cells</term><term>Monoclonal antibody</term><term>National defense</term><term>Ngrmlq ionomycin</term><term>Pathway</term><term>Peripheral blood</term><term>Pharmacol</term><term>Pharmacology</term><term>Protein kinase</term><term>Protein kinase effect</term><term>Receptor</term><term>Room temperature</term><term>Tetrandrine</term><term>Therapeutic effect</term><term>Thong</term><term>Various concentrations</term><term>Various times</term></keywords></textClass><langUsage><language ident="en">en</language></langUsage></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Abstract: Tetrandrine, a purified traditional Chinese medicinal herb that acts as an immunosuppressant and a Ca2+ channel blocker, has been clinically used to treat patients with 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 on 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 the T cell activation antigen, CD71. Further investigation of the molecular mechanism demonstrated that tetrandrine inhibited the expression of the protein kinase C-dependent interleukin-2 receptor alpha chain and CD69 but not the expression of the Ca2+-dependent CD40 ligand and CD69. Interestingly, when tetrandrine and cyclosporin A were added together, significant synergism in the 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 concentrations, 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.</div></front></TEI><affiliations><list><country><li>République populaire de Chine</li></country></list><tree><country name="République populaire de Chine"><noRegion><name sortKey="Ho, Ling Jun" sort="Ho, Ling Jun" uniqKey="Ho L" first="Ling-Jun" last="Ho">Ling-Jun Ho</name></noRegion><name sortKey="Chang, Deh Ming" sort="Chang, Deh Ming" uniqKey="Chang D" first="Deh-Ming" last="Chang">Deh-Ming Chang</name><name sortKey="Chang, Mu Lan" sort="Chang, Mu Lan" uniqKey="Chang M" first="Mu-Lan" last="Chang">Mu-Lan Chang</name><name sortKey="Lai, Jenn Haung" sort="Lai, Jenn Haung" uniqKey="Lai J" first="Jenn-Haung" last="Lai">Jenn-Haung Lai</name><name sortKey="Lee, Ta Chung" sort="Lee, Ta Chung" uniqKey="Lee T" first="Ta-Chung" last="Lee">Ta-Chung Lee</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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