TY - JOUR
T1 - Differential expression of CX3CL1 in hepatitis B virus-replicating hepatoma cells can affect the migration activity of CX3CR1+ immune cells
AU - Kondo, Yasuteru
AU - Kimura, Osamu
AU - Tanaka, Yasuhito
AU - Ninomiya, Masashi
AU - Iwata, Tomoaki
AU - Kogure, Takayuki
AU - Inoue, Jun
AU - Sugiyama, Masaya
AU - Morosawa, Tatsuki
AU - Fujisaka, Yasuyuki
AU - Shimosegawa, Tooru
N1 - Publisher Copyright:
© 2015, American Society for Microbiology.
PY - 2015
Y1 - 2015
N2 - In addition to stellate cells and immune cells, inflamed hepatocytes and hepatoma cells express various kinds of chemokines that attract various kinds of immune cells. Previously, we reported that hepatitis B virus (HBV) replication can induce physiological stress. The aim of this study was to analyze the effect of chemokines produced by HBV-infected hepatocytes and hepatoma cells. A real-time PCR array targeting genes related to chemokines and enzyme-linked immunosorbent assay (ELISA) were carried out to detect the specific chemokines produced by Huh7 cells and HepG2 cells infected with various HBV genotypes. A migration assay, flow cytometry analysis, and immunohistochemistry were carried out to analyze the candidate immune cells that can affect the immunopathogenesis of HBV infection. The expressions of CX3CL1 mRNA and protein were significantly different among HBV genotypes A, B, and C and control cells (mock) (P<0.05). CD56+ NK cells and CD8+ T cells migrated to the hepatoma cells with HBV replication. Moreover, the migration activity of both immune cells was partially cancelled after the treatment of CX3CL1 neutralizing antibody. The expression level of NKG2D on CX3CR1+ NK cells in HCC with HBV infection was significantly lower than that in hepatocellular carcinoma (HCC) with HCV infection and chronic hepatitis B and C patients (P<0.05). On the other hand, the frequency of PD-1high CX3CR1+ CD8+ T cells in HCC with HBV infection was significantly higher than that in HCC with HCV infection and chronic hepatitis B and C (P<0.05). The expression of CX3CL1 in HBV-replicating hepatocytes and hepatoma cells could contribute to the immunopathogenesis of HBV infection.
AB - In addition to stellate cells and immune cells, inflamed hepatocytes and hepatoma cells express various kinds of chemokines that attract various kinds of immune cells. Previously, we reported that hepatitis B virus (HBV) replication can induce physiological stress. The aim of this study was to analyze the effect of chemokines produced by HBV-infected hepatocytes and hepatoma cells. A real-time PCR array targeting genes related to chemokines and enzyme-linked immunosorbent assay (ELISA) were carried out to detect the specific chemokines produced by Huh7 cells and HepG2 cells infected with various HBV genotypes. A migration assay, flow cytometry analysis, and immunohistochemistry were carried out to analyze the candidate immune cells that can affect the immunopathogenesis of HBV infection. The expressions of CX3CL1 mRNA and protein were significantly different among HBV genotypes A, B, and C and control cells (mock) (P<0.05). CD56+ NK cells and CD8+ T cells migrated to the hepatoma cells with HBV replication. Moreover, the migration activity of both immune cells was partially cancelled after the treatment of CX3CL1 neutralizing antibody. The expression level of NKG2D on CX3CR1+ NK cells in HCC with HBV infection was significantly lower than that in hepatocellular carcinoma (HCC) with HCV infection and chronic hepatitis B and C patients (P<0.05). On the other hand, the frequency of PD-1high CX3CR1+ CD8+ T cells in HCC with HBV infection was significantly higher than that in HCC with HCV infection and chronic hepatitis B and C (P<0.05). The expression of CX3CL1 in HBV-replicating hepatocytes and hepatoma cells could contribute to the immunopathogenesis of HBV infection.
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U2 - 10.1128/JVI.00716-15
DO - 10.1128/JVI.00716-15
M3 - Article
C2 - 25926643
AN - SCOPUS:84958943888
SN - 0022-538X
VL - 89
SP - 7016
EP - 7027
JO - Journal of Virology
JF - Journal of Virology
IS - 14
ER -
