CpG ODN pretreatment attenuates concanavalin A-induced hepatitis in mice.

CpG ODN pretreatment attenuates concanavalin A-induced hepatitis in mice.
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DOI:
10.1016/j.intimp.2009.09.025
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发表时间:
2010
影响因子:
5.6
通讯作者:
Hui Zhang;Q. Gong;Jun-hua Li;Xiao-ling Kong;Li Tian;L. Duan;Jing Tong;Fei-fei Song;M. Fang;F. Zheng;P. Xiong;Z. Tan;F. Gong
Hui Zhang;Q. Gong;Jun-hua Li;Xiao-ling Kong;Li Tian;L. Duan;Jing Tong;Fei-fei Song;M. Fang;F. Zheng;P. Xiong;Z. Tan;F. Gong
中科院分区:
医学2区
文献类型:
--
作者:
Hui Zhang;Q. Gong;Jun-hua Li;Xiao-ling Kong;Li Tian;L. Duan;Jing Tong;Fei-fei Song;M. Fang;F. Zheng;P. Xiong;Z. Tan;F. Gong

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T细胞介导的肝损伤在自身免疫性肝炎、病毒性肝炎和急性肝衰竭等肝病的发病机制中起着关键作用。含CpG的寡脱氧核苷酸(CpG ODN)是Toll样受体9(TLR 9)的配体,广泛用作免疫佐剂。在本研究中,我们研究了CpG ODN对伴刀豆球蛋白A(Con A)诱导的小鼠肝炎模型中T细胞介导的肝损伤的影响。结果发现,CpG ODN预处理小鼠的转氨酶水平明显降低,小鼠的存活时间明显延长。CpG ODN预处理抑制NF-κB DNA结合活性。结果,全身/肝脏的TNF-α和IFN-γ水平被显着抑制。此外,CpG ODN预处理可抑制炎症细胞的活化。提示CpG ODN预处理对ConA诱导的小鼠肝损伤具有保护作用,其机制可能与抑制肝细胞凋亡、炎症反应和淋巴细胞活化有关。
T cell-mediated hepatic damage plays a key role in the pathogenesis of liver diseases such as autoimmune hepatitis, viral hepatitis and acute liver failure. CpG-containing oligodeoxynucleotides (CpG ODN), a ligand for toll-like receptor (TLR) 9, is widely used as an immunological adjuvant. In the present study, we investigated the effect of CpG ODN on T cell-mediated liver injury in a murine model of concanavalin A (Con A)-induced hepatitis. We found that the aminotransferase level was significantly decreased in CpG ODN pretreated mice and the survival of the mice was markedly prolonged. CpG ODN pretreatment inhibited NF-κB DNA binding activity. As a result, the systemic/liver levels of TNF-α and IFN-γ were significantly suppressed. Furthermore, the activation of inflammatory cells was diminished by CpG ODN pretreatment. These results suggest that CpG ODN pretreatment protects the mice from Con A-induced liver injury via inhibiting hepatocyte apoptosis, inflammation and activation of lymphocytes.