Baohuoside-1, a Novel Immunosuppressive Molecule, Inhibits Lymphocyte Activation In Vitro and In Vivo
| Autor: | Anlun Ma, Shijie Qi, Dasheng Xu, Pierre Daloze, Huifang Chen, Xiaochun Zhang |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Male
Lymphocyte Lymphocyte proliferation In Vitro Techniques Pharmacology Biology Lymphocyte Activation chemistry.chemical_compound In vivo medicine Animals Humans Flavonoids Transplantation CD28 Mixed lymphocyte reaction Rats Kinetics medicine.anatomical_structure Biochemistry Mechanism of action chemistry Rats Inbred Lew Ionomycin Phorbol Tetradecanoylphorbol Acetate Lymphocyte Culture Test Mixed Mitogens medicine.symptom Cell Division Immunosuppressive Agents Drugs Chinese Herbal |
| Zdroj: | Transplantation. 78:831-838 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/01.tp.0000137786.56231.41 |
| Popis: | Background. We evaluated the in vitro and in vivo immunosuppressive effects of baohuoside- 1 ( B1), a novel flavonoid isolated from Epimedium davidii. Methods. Proliferation assay was used to determine the antiproliferative properties on T-cell and B-cell proliferation. Flow cytometry analysis was applied to detect changes of phenotypes on activated cells. Results. B1 inhibits the lymphocyte proliferation activated by polyclonal mitogens and mixed lymphocyte reaction with a 50% inhibitory concentration of low micromolar concentration. Also, B1 suppressed T-cell activation in T cell receptor/CD3-mediated signaling pathways in a dose- and time-dependent manner. The suppression of B1 was not simply a result of a toxic effect and was recovered by withdrawing the drug. B1 down-regulated the expression of some phenotype molecules. In Ca 2+ -independent or -dependent antigen stimulation, although B1 had different inhibitive patterns on CD69 expression stimulated by phorbol 12-myristate 13-acetate (PMA) or Ca 2+ ionophore, it inhibited T-cell proliferation induced by CD3/CD28 or PMA/ionomycin and partially blocked that induced by PMA/CD28. Interestingly, an additive inhibition between B 1 and tacrolimus (FK506) was found in the CD69 expression stimulated by PMA/CD28 and PMA/ionomycin. Similarly, this immunosuppression by combination therapy was observed in a heart transplantation model in vivo and might act through an immunosuppressive mechanism different from FK506. Conclusions. B1, whose mechanism of action is not similar to that of FK506, has selectively immunosuppressive effects on T-cell and B-cell activation in vitro and effectively prevents rat heart allograft rejection in vivo. |
| Databáze: | OpenAIRE |
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