1. SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo.
- Author
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Hou LF, He SJ, Wang JX, Yang Y, Zhu FH, Zhou Y, He PL, Zhang Y, Yang YF, Li Y, Tang W, and Zuo JP
- Subjects
- Administration, Oral, Animals, Antibodies, Monoclonal, Antigens, CD biosynthesis, Antigens, CD immunology, Apoptosis drug effects, Apoptosis immunology, Artemisinins pharmacology, CD4-Positive T-Lymphocytes immunology, CD4-Positive T-Lymphocytes metabolism, CD4-Positive T-Lymphocytes pathology, Cell Proliferation drug effects, Cells, Cultured, Female, Immunization, Lymphocyte Activation drug effects, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Ovalbumin immunology, T-Cell Antigen Receptor Specificity immunology, Artemisinins administration & dosage, CD4-Positive T-Lymphocytes drug effects, Immunosuppressive Agents administration & dosage, Interferon-gamma metabolism, Proto-Oncogene Proteins c-akt metabolism
- Abstract
In the present study, we investigated the immunosuppressive effects and underlying mechanisms of beta-aminoarteether maleate (SM934), a derivative of artemisinin, against T cell activation in vitro and in vivo. In vitro, SM934 significantly inhibited the proliferation of splenocytes induced by concanavalin A (Con A), lipopolysaccharide (LPS), mixed lymphocyte reaction (MLR), and anti-CD3 plus anti-CD28 (anti-CD3/28). SM934 significantly inhibited interferon (IFN)-gamma production and CD4(+) T cell division stimulated by anti-CD3/28. SM934 also promoted apoptosis of CD69(+) population in CD4(+) T cells stimulated by anti-CD3/28. Furthermore, SM934 inhibited interleukin (IL)-2 mediated proliferation and survival through blocking Akt phosphorylation in activated T cells. In ovalbumin (OVA)-immunized mice, oral administration of SM934 suppressed OVA-specific T cell proliferation and IFN-gamma production. SM934 treatment also significantly inhibited the sheep red blood cell (SRBC)-induced delayed type hypersensitivity (DTH) reactions in mice. Taken together, SM934 showed potent immunosuppressive activities in vitro and in vivo. Our results demonstrated that SM934 might be a potential therapeutic agent for immune-related diseases.
- Published
- 2009
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