CpG ODN pretreatment attenuates concanavalin A-induced hepatitis in mice.
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-kappaB DNA binding activity. As a result, the systemic/liver levels of TNF-alpha and IFN-gamma 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.
Zhang
Hui
H
Department of Immunology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
Gong
Quan
Q
Li
Jun-hua
JH
Kong
Xiao-ling
XL
Tian
Li
L
Duan
Li-hua
LH
Tong
Jing
J
Song
Fei-fei
FF
Fang
Min
M
Zheng
Fang
F
Xiong
Ping
P
Tan
Zheng
Z
Gong
Fei-li
FL
D000818:Animals; D002460:Cell Line; D002469:Cell Separation; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000276:immunology; D003208:Concanavalin A / Q000633:toxicity; D004336:Drug Antagonism; D005434:Flow Cytometry; D006505:Hepatitis / Q000188:drug therapy* / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008934:Mitogens / Q000633:toxicity; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism*; D020319:Oligodeoxyribonucleotides, Antisense / Q000008:administration & dosage; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D008934:Mitogens; D016328:NF-kappa B; D020319:Oligodeoxyribonucleotides, Antisense; D014409:Tumor Necrosis Factor-alpha; D003208:Concanavalin A; D007371:Interferon-gamma