TY - JOUR
T1 - Lipopolysaccharide-induced innate immune responses in primary hepatocytes downregulates woodchuck hepatitis virus replication via interferon-independent pathways
AU - Zhang, Xiaoyong
AU - Meng, Zhongji
AU - Qiu, Song
AU - Xu, Yang
AU - Yang, Dongliang
AU - Schlaak, Jörg F.
AU - Roggendorf, Michael
AU - Lu, Mengji
PY - 2009/11
Y1 - 2009/11
N2 - Our previous studies have shown that Toll-like receptor (TLR) ligands, Poly I:C and lipopolysaccharide (LPS), are able to activate nonparenchymal liver cells and trigger the production of interferon (IFN) to inhibit hepatitis B virus replication in vivo and in vitro. However, little is known about TLR-mediated cellular responses in primary hepatocytes. By the model of woodchuck hepatitis virus (WHV) infected primary woodchuck hepatocytes (PWHs), Poly I:C and LPS stimulation resulted in upregulation of cellular antiviral genes and relevant TLRs mRNA expression respectively. LPS stimulation led to a pronounced reduction of WHV replicative intermediates without a significant IFN induction. Poly I:C transfection resulted in the production of IFN and a highly increased expression of antiviral genes in PWHs and slight inhibitory effect on WHV replication. LPS could activate nuclear factor kappa B, MAPK and PI-3k/Akt pathways in PWHs. Further, inhibitors of MAPK-ERK and PI-3k/Akt pathways, but not that of IFN signalling pathway, were able to block the antiviral effect of LPS. These results indicate that IFNindependent pathways which activated by LPS are able to downregulate hepadnaviral replication in hepatocytes.
AB - Our previous studies have shown that Toll-like receptor (TLR) ligands, Poly I:C and lipopolysaccharide (LPS), are able to activate nonparenchymal liver cells and trigger the production of interferon (IFN) to inhibit hepatitis B virus replication in vivo and in vitro. However, little is known about TLR-mediated cellular responses in primary hepatocytes. By the model of woodchuck hepatitis virus (WHV) infected primary woodchuck hepatocytes (PWHs), Poly I:C and LPS stimulation resulted in upregulation of cellular antiviral genes and relevant TLRs mRNA expression respectively. LPS stimulation led to a pronounced reduction of WHV replicative intermediates without a significant IFN induction. Poly I:C transfection resulted in the production of IFN and a highly increased expression of antiviral genes in PWHs and slight inhibitory effect on WHV replication. LPS could activate nuclear factor kappa B, MAPK and PI-3k/Akt pathways in PWHs. Further, inhibitors of MAPK-ERK and PI-3k/Akt pathways, but not that of IFN signalling pathway, were able to block the antiviral effect of LPS. These results indicate that IFNindependent pathways which activated by LPS are able to downregulate hepadnaviral replication in hepatocytes.
UR - http://www.scopus.com/inward/record.url?scp=72049087654&partnerID=8YFLogxK
U2 - 10.1111/j.1462-5822.2009.01353.x
DO - 10.1111/j.1462-5822.2009.01353.x
M3 - Article
C2 - 19573162
AN - SCOPUS:72049087654
SN - 1462-5814
VL - 11
SP - 1624
EP - 1637
JO - Cellular Microbiology
JF - Cellular Microbiology
IS - 11
ER -
