In vitro tumor necrosis factor cytotoxicity in Hep G2 liver cells - PubMed (original) (raw)
Affiliations
- PMID: 7535734
In vitro tumor necrosis factor cytotoxicity in Hep G2 liver cells
D B Hill et al. Hepatology. 1995 Apr.
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. We suggest that the Hep G2 cell line sensitized by inhibiting RNA and protein synthesis is a useful in vitro model for evaluating mechanism(s) of TNF-mediated liver cell injury.
Similar articles
- TNF-alpha-induced cell death in ethanol-exposed cells depends on p38 MAPK signaling but is independent of Bid and caspase-8.
Pastorino JG, Shulga N, Hoek JB. Pastorino JG, et al. Am J Physiol Gastrointest Liver Physiol. 2003 Sep;285(3):G503-16. doi: 10.1152/ajpgi.00442.2002. Epub 2003 May 14. Am J Physiol Gastrointest Liver Physiol. 2003. PMID: 12748063 - Self-induction of defense against tumor necrosis factor cytotoxicity in tumor cells and normal cells.
Watanabe N, Neda H, Yamauchi N, Maeda M, Sone H, Kuriyama H, Niitsu Y. Watanabe N, et al. Immunopharmacol Immunotoxicol. 1988;10(4):479-99. doi: 10.3109/08923978809006450. Immunopharmacol Immunotoxicol. 1988. PMID: 3246539 - Influence of tumor necrosis factor-alpha and silibin on the cytotoxic action of alpha-amanitin in rat hepatocyte culture.
El-Bahay C, Gerber E, Horbach M, Tran-Thi QH, Röhrdanz E, Kahl R. El-Bahay C, et al. Toxicol Appl Pharmacol. 1999 Aug 1;158(3):253-60. doi: 10.1006/taap.1999.8705. Toxicol Appl Pharmacol. 1999. PMID: 10438658
Cited by
- Combined obeticholic acid and apoptosis inhibitor treatment alleviates liver fibrosis.
Zhou J, Huang N, Guo Y, Cui S, Ge C, He Q, Pan X, Wang G, Wang H, Hao H. Zhou J, et al. Acta Pharm Sin B. 2019 May;9(3):526-536. doi: 10.1016/j.apsb.2018.11.004. Epub 2018 Nov 27. Acta Pharm Sin B. 2019. PMID: 31193776 Free PMC article. - TNF Tolerance in Monocytes and Macrophages: Characteristics and Molecular Mechanisms.
Huber R, Bikker R, Welz B, Christmann M, Brand K. Huber R, et al. J Immunol Res. 2017;2017:9570129. doi: 10.1155/2017/9570129. Epub 2017 Nov 8. J Immunol Res. 2017. PMID: 29250561 Free PMC article. Review. - S-adenosylhomocysteine inhibits NF-κB-mediated gene expression in hepatocytes and confers sensitivity to TNF cytotoxicity.
Watson WH, Burke TJ, Doll MA, McClain CJ. Watson WH, et al. Alcohol Clin Exp Res. 2014 Apr;38(4):889-96. doi: 10.1111/acer.12315. Epub 2013 Nov 13. Alcohol Clin Exp Res. 2014. PMID: 24224954 Free PMC article. - Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase reactant.
Liu Z, Ukomadu C. Liu Z, et al. Biochem Biophys Res Commun. 2008 Jan 25;365(4):729-34. doi: 10.1016/j.bbrc.2007.11.069. Epub 2007 Nov 26. Biochem Biophys Res Commun. 2008. PMID: 18039467 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources