Bicyclol attenuates pro-inflammatory cytokine and chemokine productions in CpG-DNA-stimulated L02 hepatocytes by inhibiting p65-NF-kappaB and p38-MAPK activation.
Bicyclol, a novel synthetic anti-hepatitis drug, has a potent hepatocyte-protective effect and a mild anti-hepatitis virus function. However, its pharmaceutical effects and mechanism are still unclear. In the present study, we found that bicyclol pre-treatment could attenuate the production of the inflammatory cytokines (TNF-alpha and IL-18) and chemokines (MCP-1, MIP-1 alpha and Rantes) and inhibit the activation of the p65-NF-kappaB and MAPK signaling pathways in CpG-ODN 2006-stimulated L02 hepatocytes in a dose-dependent manner. Collectively, these results suggest that bicyclol could exert its hepatocyte-protective effect through attenuating CpG-ODN 2006-stimulated inflammatory responses in L02 hepatocytes, which might be associated with the activations of NF-kappaB and MAPK pathways.
Lou
Xiao-E
XE
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Xu
Ning
N
Yao
Hang-Ping
HP
Chen
Zhi
Z
D001713:Biphenyl Compounds / Q000494:pharmacology*; D015153:Blotting, Western; D018925:Chemokines / Q000096:biosynthesis*; D018899:CpG Islands; D016207:Cytokines / Q000096:biosynthesis*; D004247:DNA / Q000494:pharmacology*; D004279:DNA, Viral / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism*; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D015398:Signal Transduction / Q000187:drug effects; D013268:Stimulation, Chemical; D051217:Toll-Like Receptor 9 / Q000502:physiology; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*
D001713:Biphenyl Compounds; D018925:Chemokines; D016207:Cytokines; D004279:DNA, Viral; D009687:Nuclear Proteins; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; D051996:Transcription Factor RelA; D004247:DNA; C477843:bicyclol; D048051:p38 Mitogen-Activated Protein Kinases