PMID: 7535734Apr 1, 1995Paper

In vitro tumor necrosis factor cytotoxicity in Hep G2 liver cells

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Daniell B HillC J McClain

Abstract

Tumor necrosis factor-alpha (TNF-alpha) is a mediator of liver injury. The objective of this study was to develop an in vitro model of TNF-mediated liver cell injury using the Hep G2 cell line. Hep G2 cells normally are insensitive to TNF cytotoxicity, but they were rendered susceptible, or sensitized, to TNF cytotoxicity by inhibitors of RNA and protein synthesis. The concentration of TNF required to kill 50% of Hep G2 cells sensitized with 0.8 mumol/L actinomycin D (Act D) was 35 pmol/L compared with 5 pmol/L for LM fibroblasts, a classic target cell used in TNF cytotoxicity bioassays. Similarly, TNF cytotoxicity occurred in Hep G2 cells sensitized with cycloheximide (CHX), and cytotoxicity to both inhibitors was dose dependent. Both protein and RNA synthesis were inhibited in Hep G2 cells by the concentrations of CHX and Act D associated with TNF cytotoxicity. Hep G2 cells pretreated with TNF alone and later exposed to normally toxic concentrations of TNF with DACT did not develop cytotoxicity. Thus, in vitro tolerance to TNF was induced. Cytotoxicity also was more severe at modestly increased temperatures (39 degrees C versus 37 degrees C), which may have clinical relevance to hepatic decompensation during febrile episodes....Continue Reading

References

Jul 1, 1992·The Journal of Clinical Investigation·W A Border, E Ruoslahti
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Feb 1, 1991·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·A KhorutsJ I Allen
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Nov 1, 1990·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·I HishinumaI Yamatsu
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May 1, 1993·Seminars in Liver Disease·C McClainA M Diehl

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Citations

Mar 1, 2012·Archives of Toxicology·Leon AnArthur I Cederbaum
Nov 5, 1999·Cytokine·M N DevalarajaD B Hill
Nov 28, 2007·Biochemical and Biophysical Research Communications·Zhilin Liu, Chinweike Ukomadu
Dec 19, 2017·Journal of Immunology Research·René HuberKorbinian Brand

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