SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo.
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.
Hou
Li-Fei
LF
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
He
Shi-Jun
SJ
Wang
Jun-Xia
JX
Yang
Yang
Y
Zhu
Feng-Hua
FH
Zhou
Yu
Y
He
Pei-Lan
PL
Zhang
Yu
Y
Yang
Yi-Fu
YF
Li
Ying
Y
Tang
Wei
W
Zuo
Jian-Ping
JP
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
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