Double-stranded RNA and bacterial lipopolysaccharide enhance sensitivit to TNF-{alpha}-mediated cell death |
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Authors: | Gromkowski, Stanislaw H. Mama, Khuzaima Yagi, Junji Sen, Ranjan Rath, Satyajit |
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Affiliation: | Section of Immunobiology, Howard Hughes Medical Institute at Yale University School Medicine New Haven, Ct 06510, USA 1 Rosenstiel center, Department of Biology, Brandes University Waltham, MA 02254, USA |
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Abstract: | The effect of double-stranded RNA (dsRNA) and bacterial lipopolysaccharideon the sensitivity to tumor necrosis factor (TNF)--medlatedcell death was studied In an In vitro system. Since secretionof TNF- Is a part of the early host response to viral and bacterialinfection, we examined whether mimicking the Infection withviral and bacterial products could affect the response of cellsto TNF-. Incubation of WEHI 164 fibrosarcoma cells with dsRNAor lipopolysaccharide (LPS) significantly increased their sensitivityto TNF--mediated lysis and to TNF-secreting inflammatory T cell-mediatedlysis. Thus, these products could induce Increased sensitivityto TNF- In cells In an inflammatory focus, possibly contributingto selective elimination of Infected but not healthy cells bythis non-specific cytokine. Additionally, our data show thatboth dsRNA and LPS, as well as TNF- Itself, rapidly Induce nuclearfactor-xB (NF-*B), a DNA-bindlng protein Implicated In regulationof gene expression. We suggest that NF-xB could regulate genescrucial for the induction of cell death by TNF-. |
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Keywords: | inflammation NF-XB inflammation T cells |
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