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Bingjie Gu,Yanying Zeng,Cheng Yin,Huijiuan Wang,Xiaofan Yang,Song Wang,Xiaohui Ji.Journal of Biomedical Research,2012,26(6):448-455
Sinomenine reduces iNOS expression via inhibiting the T-bet IFN-pathway in experimental autoimmune encephalomyelitis in rats
Received:October 07, 2011  
DOI10.7555/JBR.26.20110114
Keywordssinomenine, experimental autoimmune encephalomyelitis, iNOS, T-bet, interferon- (IFN-)
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Bingjie Gu Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu , China
Yanying Zeng Department of Neurology, the First Affiliated Hospital, Nanjing Medical University, Nanjing, Jiangsu , China
Cheng Yin Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu , China
Huijiuan Wang Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu , China
Xiaofan Yang Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu , China
Song Wang Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu , China
Xiaohui Ji Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu , China
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Abstract
      Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal plant Sinomenium acutum. It is widely used as an immunosuppressive drug for treating rheumatic and arthritic diseases. In our previous studies, we found that sinomenine reduced cellular infiltration within the spinal cord and alleviated experimental autoimmune encephalomyelitis (EAE) in rats. In this study, we further investigated the mechanisms of sinomenine treatment in EAE rats. In EAE rats, treatment with sinomenine exerted an anti-inducible NO synthase (anti-iNOS) effect, which is related to the reductions of Th1 cytokine interferon- (IFN-) and its transcription factor, T-bet, in spinal cords. Moreover, sinomenine treatment of splenocytes stimulated with anti-CD3 antibody and recombinant rat in-terleukin 12 reduced the expression of T-bet and IFN- in vitro and also reduced the capability of supernatants of splenocyte culture to induce iNOS expression by primary astrocytes. However, sinomenine had no direct inhibito-ry effect on iNOS produced by astrocytes cultured with IFN- and tumor necrosis factor in vitro. In conclusion, the anti-iNOS effect of sinomenine on EAE is mediated via the suppression of T-bet /IFN- pathway.
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