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R Beyaert

Publications and source records attributed to R Beyaert.

74 records · Page 5Linked to original sources
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TNF in combination with interferon-gamma is cytotoxic to normal, untransformed mouse and rat embryo fibroblast-like cells.

The cytostatic and cytolytic effects of the combination of Tumour Necrosis Factor (TNF) and Interferon-gamma (IFN-gamma) on freshly isolated, untransformed and non-tumorigenic mouse embryo fibroblast-like (MEF) as well as rat embryo fibroblast-like (REF) cells are reported. Both TNF and IFN-gamma decreased the proliferation rate of REF cells, and prolonged treatment with the combination of TNF and IFN-gamma was cytolytic to the cells. IFN-gamma alone also inhibited the growth of MEF cells, an activity not shared by TNF, and was even cytolytic after treatment for more than one week. Growth inhibition as well as cytolysis of MEF cells by IFN-gamma was strongly enhanced by TNF. This is one of the few reports regarding the cytotoxic action of the combination of recombinant TNF and IFN-gamma on untransformed cells.

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TNF-induced intracellular signaling leading to gene induction or to cytotoxicity by necrosis or by apoptosis.

TNF-induced apoptosis, e.g. in murine PC60 cells, requires the TNF receptor p55 (TNF-R55) and the TNF receptor p75 (TNF-R75); the latter even does not have to be triggered. The intracellular domain of TNF-R55 can be activated in the cytosol by linking it to the trimeric CAT protein; induction of this fusion protein leads to a full TNF response. A new MAP kinase, p38, has been shown to be also activated by TNF. This activation is essential for gene induction, but not for cytotoxicity in L929 cells. TNF treatment of L929 leads to reactive oxygen formation in the mitochondria, resulting in cell death by necrosis. TNF treatment of many other cell types results in apoptosis, and this process involves activation of one or more ICE homologs (IHO). In the mouse, seven cysteine proteases of the IHO family have been cloned and partially characterized. One or more of these IHOs is involved in cell killing by proteolysis of critical substrate(s). One substrate, which may be a key effector molecule in the apoptotic process, is PITSLRE kinase.

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