Rabbit tumor necrosis factor: mechanism of action

Ruff, Michael R.; Gifford, George E.

doi:10.1128/iai.31.1.380-385.1981

Cited by 180 publications

(24 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These data suggest an important role for TNF inducible genes, which protect against further cell types. 13,20,21,23,25,35 hepatic TNF toxicity. Thus, hepatocyte TNF tolerance was induced in uitro in these cells without having to invoke other mechanisms that can occur in uiuo, such as the release of hormones or inhibitory cytokines by other cell types.…”

Section: Discussionmentioning

confidence: 99%

In vitro tumor necrosis factor cytotoxicity in HEP G2 liver cells

et al. 1995

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

In vitro tumor necrosis factor cytotoxicity in HEP G2 liver cells

et al. 1995

View full text Add to dashboard Cite

show abstract

“…Thioglycollate-elicited macrophages from diet mice were plated in 96-well dishes and treated LINSEED OIL EFFECTS ON MACROPHAGE FUNCTION with LPS, as just described. After the activation period, supernatants of monolayers were tested for TNFa content by using a bioassay with the TNFa-sensitive cell line L929, as described (2,17). For the bioassay, sample supernatants or rTNFa standard were added in triplicate to 96well plates containing 2-3 x 104 adherent L929 cells.…”

Section: Methodsmentioning

confidence: 99%

Effect of dietary linseed oil on tumoricidal activity and eicosanoid production in murine macrophages

Hubbard

Chapkin

Erickson

1994

Lipids

View full text Add to dashboard Cite

Diets that contain high levels of n-3 fatty acids from fish oil have been shown to significantly effect macrophage cytolytic capacity, tumor necrosis factor alpha production and eicosanoid production. The present study was undertaken to determine whether n-3 fatty acids from vegetable origin [linseed oil (LIN)] would have the same effects on murine macrophage tumoricidal capacity and eicosanoid production as would fish oil. Mice were fed for three weeks diets that contained 10% (wt/wt) of either LIN, which is high in linolenic acid (18:3n-3), menhaden fish oil (MFO), which is high in eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) acids, or safflower oil (SAF), which is high in linoleic acid (18:2n-6). In vivo- or in vitro-activated macrophages were assessed for select functions. As expected, macrophages from mice fed LIN and MFO produced significantly lower levels of both prostaglandins and leukotriene C4 when compared with macrophages from mice fed SAF. In addition, LIN and MFO macrophages were able to synthesize leuko-triene C5, which could not be produced by macrophages from mice fed SAF. The effects of LIN, however, were not as pronounced as those of MFO. With respect to specific functions, macrophages from mice fed LIN did not have altered cytolytic capacity when compared with macrophages from mice fed SAF and activated in vitro with either lipopolysaccharide (LPS) alone for 24 h or with LPS plus interferon gamma (IFN gamma) for 5 h. Diet did not significantly alter tumoricidal capacity of macrophages activated completely in vivo either.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

“…Unlike developmental apoptosis, TNFa-mediated cell death is not dampened by inhibitors of protein or RNA synthesis, showing that no synthesis of new proteins is required. On the contrary, the sensitivity to TNFa is greatly increased by treating the target cells with macromoleeular synthesis inhibitors, such as actinomycin D or cycloheximide (Ruff & Gifford 1981), implying that the cells can prevent TNFa-mediated damage by synthesizing new protective proteins. For example, human fibroblasts are resistant to TNFa alone but are rendered sensitive if treated with TNFa in combination with cycioheximide (Kirstein & Baglioni 1986).…”

Section: Tnfa-mediated Cell Deathmentioning

confidence: 99%

Cell Death Mechanisms and the Immune System

Golstein

Ojcius

Young

1991

Immunological Reviews

428

171

View full text Add to dashboard Cite

The immune system provides good models for cell death, a phenomenon now recognized to be of fundamental importance in many fields of biology. Cell death is strikingly polymorphic: it can proceed via necrosis (as in complement-mediated cell death) or apoptosis, but the latter displays different patterns (in the receptor-mediated death of some thymocytes, in cell death mediated by TNF alpha or by cytotoxic T cells), perhaps reflecting different pathways of control of a common core mechanism. Even though there are differences in the morphological and metabolic changes associated with the different patterns of apoptosis, some recurrent sequences of events are observed in almost all dying cells. The metabolic state of a cell often seems to play a major role in determining if and how this cell will die in given external circumstances. The nature of molecules causally involved in the dying cell can now be approached in some systems.

show abstract

Rabbit tumor necrosis factor: mechanism of action

Cited by 180 publications

References 17 publications

In vitro tumor necrosis factor cytotoxicity in HEP G2 liver cells

In vitro tumor necrosis factor cytotoxicity in HEP G2 liver cells

Effect of dietary linseed oil on tumoricidal activity and eicosanoid production in murine macrophages

Cell Death Mechanisms and the Immune System

Contact Info

Product

Resources

About