Article

SM934, a water-soluble derivative of arteminisin, exerts immunosuppressive functions in vitro and in vivo

State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, People's Republic of China.
International immunopharmacology (Impact Factor: 2.71). 09/2009; 9(13-14):1509-17. DOI: 10.1016/j.intimp.2009.09.003
Source: PubMed

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.

Download full-text

Full-text

Available from: Lifei Hou, Jul 27, 2015
0 Followers
 · 
215 Views
  • Source
    • "Similar to SM735, the studies in Zuo group in SIMM found SM905 possessed potent immunoregulatory properties [5] [6] [7]. However, SM934 is quite distinct [11]. Similar to SM905 and artemether, in vitro, SM934 significantly inhibited the proliferation and IFN-í µí»¾ production of splenocytes or purified CD4+ T cells induced by mixed lymphocyte reaction (MLR) or TCR cross-linking. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Artemisinin and its derivatives are widely used in the world as the first-line antimalarial drug. Recently, growing evidences reveal that artemisinin and its derivatives also possess potent anti-inflammatory and immunoregulatory properties. Meanwhile, researchers around the world are still exploring the unknown bioactivities of artemisinin derivatives. In this review, we provide a comprehensive discussion on recent advances of artemisinin derivatives affecting inflammation and autoimmunity, the underlying molecular mechanisms, and also drug development of artemisinins beyond antimalarial functions.
    Mediators of Inflammation 01/2015; 2015. DOI:10.1155/2015/435713 · 3.24 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Artemisinins in combination with other antimalarial drugs remain the mainstay of current antimalarial armamentarium. It is interesting to note that many traditional drugs with antiprotozoal background can wield immunomodulation on the recipient's immune system in a positive or negative direction. Artemisinins also attribute immunomodulatory distensions. For instance, they demonstrate predominant immunosuppressive traits toward different immune components by particularly regulating the cellular proliferation and cytokine release, which indicates that they possess some additional mechanisms and features demanding deliberate attentions. This article reviews the data-based immunomodulatory effects of artemisinins on different immune cells including neutrophils, macrophages, splenocytes, T and B cells in conjunction with their therapeutic prospective with regard to inflammation, autoimmunity and delayed-type hypersensitivity.
    European journal of pharmacology 07/2011; 668(1-2):6-14. DOI:10.1016/j.ejphar.2011.06.044 · 2.68 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ObjectiveSM934, an artemisinin derivative, possesses potent antiproliferative and antiinflammatory properties. The aim of this study was to examine the effects and explore the mechanisms of SM934 to treat autoimmune disease in lupus-prone female MRL/lpr mice.Methods In vitro, the effects of SM934 on the activation of polyclonal CD4+ T cells and the differentiation of naive CD4+ T cells were examined. In vivo, the preventative or therapeutic effects of SM934 in MRL/lpr mice were investigated. Ex vivo, the mechanisms of treatment were explored according to the immunologic correlates of disease.ResultsIn vitro, SM934 inhibited interferon-γ (IFNγ) and interleukin-17 (IL-17) production from polyclonal CD4+ T cells activated by T cell receptor engagement and the differentiation of naive CD4+ T cells into Th1 and Th17 cells, but not Treg cells. In vivo, 12-week-old MRL/lpr mice treated with SM934 for 4 weeks showed significantly ameliorated proteinuria and renal lesion severity; decreased levels of blood urea nitrogen, serum IFNγ, and serum anti–double-stranded DNA antibodies; decreased spleen size; and a lower percentage of CD3+B220+CD4−CD8− T cells; 16-week-old MRL/lpr mice treated with SM934 for 8 weeks avoided severe proteinuria and survived longer. Ex vivo, SM934 treatment elevated the percentage of Treg cells, inhibited the development of Th1 and Th17 cells, and impeded the comprehensive activation of STAT-1, STAT-3, and STAT-5 proteins in splenocytes.Conclusion Taken together, the results of this study demonstrated that the artemisinin analog SM934 had therapeutic effects in lupus-prone female MRL/lpr mice by inhibiting both Th1 cell and Th17 cell responses. Moreover, this study indicated that both IFNγ and IL-17 are required for the elicitation and development of murine lupus.
    Arthritis & Rheumatology 08/2011; 63(8):2445 - 2455. DOI:10.1002/art.30392 · 7.87 Impact Factor
Show more