Suppressive effect of hepatitis B virus on the induction of interleukin-1 beta and interleukin-6 gene expression in the THP-1 human monocytic cell line.
The major target organ for Hepatitis B Virus (HBV) is the liver, but extrahepatic sites including monocytes express receptors for HBV and may become infected. Therefore, we investigated the effect of HBV on the in vitro expression of interleukin-beta (IL-1 beta) and interleukin-6 (IL-6) by the monocytoid cell line THP-1, exposed to various stimuli (LPS, PMA or both). Nonstimulated THP-1 cells did not synthesize IL-1 beta and IL-6, even after in vitro exposure to HBV. LPS stimulation alone induced moderate secretion of both IL-1 beta and IL-6 (300 pg/ml). After induction of macrophage differentiation by PMA, THP-1 cells acquired adherence and expressed a higher level of IL-1 beta (up to 2 ng/ml) but did not synthesize IL-6. Treatment of THP-1 cells with PMA and LPS caused the highest production of both IL-1 beta and IL-6 (> 5ng/ml). In vitro exposure of PMA + LPS-stimulated THP-1 cells to HBV resulted in secretion of both HBsAg and preS2Ag which was maintained over 10 days of culture. Southern blot technique was used to study the state of HBV DNA in the cells. Hybridization of non-digested cellular DNA showed only high molecular weight HBV DNA forms. The HindIII restriction pattern revealed bands corresponding to large DNA fragments and the presence of bands at the 3.2 kb position. Under these conditions (PMA + LPS), HBV inhibited the production of IL-1 beta and IL-6 proteins and completely suppressed the IL-1 beta and IL-6 mRNA. Thus, our findings (i) strongly support a relationship between the state of cell differentiation and susceptibility of cells to HBV infection, and (ii) demonstrate that HBV exerts an inhibitory effect on the induction of IL-1 beta and IL-6 genes expression in monocytic THP-1 cells. These results suggest that HBV leads to a fall of pro-inflammatory cytokine production by monocytes/macrophages, which may contribute to impaired host immune response during infection.
Oquendo
J
J
INSERM U 131, Clamart, France.
Dubanchet
S
S
Capel
F
F
Mabit
H
H
Petit
M A
MA
D002460:Cell Line; D004279:DNA, Viral; D015967:Gene Expression Regulation, Viral; D006515:Hepatitis B virus / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007375:Interleukin-1 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004279:DNA, Viral; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013755:Tetradecanoylphorbol Acetate