title: SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo.
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.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
authors.forename: Li-Fei
authors.initials: LF
authors.lastname: Hou
authors.forename: Shi-Jun
authors.initials: SJ
authors.lastname: He
authors.forename: Jun-Xia
authors.initials: JX
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Feng-Hua
authors.initials: FH
authors.lastname: Zhu
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Pei-Lan
authors.initials: PL
authors.lastname: He
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yi-Fu
authors.initials: YF
authors.lastname: Yang
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Tang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zuo
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D037621:Artemisinins / Q000008:administration & dosage* / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D007114:Immunization; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007371:Interferon-gamma / Q000378:metabolism*; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D037621:Artemisinins; D007166:Immunosuppressive Agents; C550182:beta-aminoarteether maleate; D007371:Interferon-gamma; D010047:Ovalbumin; D051057:Proto-Oncogene Proteins c-akt