Cytokine-mediated apoptosis and inhibition of virus production and anchorage independent growth of viral transfected hepatoblastoma cells.
Cytokine-mediated apoptotic destruction of viral-infected cells, downregulation of virus production and inhibition of anchorage dependent (clonal) cell growth were evaluated using virus-transfected human hepatoblastoma (HepG2) cells. The cytokines evaluated were interferon alpha (IFN-alpha), tumour necrosis factor alpha (TNF-alpha) and thymosin alpha 1 (T alpha 1), all of which have previously been implicated in control of various viral infections. The viruses evaluated were Hepatitis B (HBV) and the transforming virus, SV-40. TNF-alpha-induced apoptosis in the HBV-transfected cell line and the control HepG2 cells but not the HepG2 cells transfected with SV-40 virus. IFN-alpha and T alpha 1 had no effect on apoptosis. TNF-alpha also prevented the clonal growth of the HBV-HepG2 and control HepG2 but enhanced the growth of the SV-40-transfected HepG2 cells. IFN-alpha inhibited the clonal growth of all three cell lines in contrast to T alpha 1 which inhibited the clonal growth of only the HBV-transfected cells. Although TNF-alpha, IFN-alpha, and T alpha 1 when given alone did not significantly inhibit HBV-DNA production in the culture supernatant from HBV-HepG2 cells, the combination of T alpha 1 and IFN-alpha resulted in a statistically significant inhibition of virus production. These studies demonstrate that HepG2 cells transfected with HBV and SV-40 are useful for defining the mechanisms of cytokine activity. The HBV-transfected cells are especially useful in defining possible in vivo differences in responses to cytokines with respect to HBV production, apoptosis and clonal cell growth. Multiple mechanisms through which different cytokines can influence HBV infection and hepatoblastoma growth were identified and the importance of defining effective combinations to improve therapy in vivo demonstrated.
Yared
G
G
Department of Internal Medicine, Wayne State University School of Medicine, Detroit, MI, USA.
Hussain
K B
KB
Nathani
M G
MG
Moshier
J A
JA
Dosescu
J
J
Mutchnick
M G
MG
Naylor
P H
PH
D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D006515:Hepatitis B virus / Q000502:physiology*; D018197:Hepatoblastoma; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D013539:Simian virus 40 / Q000502:physiology*; D000077596:Thymalfasin; D013947:Thymosin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; D013947:Thymosin; D000077596:Thymalfasin