Double-stranded RNA and bacterial lipopolysaccharide enhance sensitivit to TNF-α -mediated cell death

The effect of double-stranded RNA (dsRNA) and bacterial lipopolysaccharide on the sensitivity to tumor necrosis factor (TNF)-α-medlated cell death was studied In an In vitro system. Since secretion of TNF-α Is a part of the early host response to viral and bacterial infection, we examined whether mimicking the Infection with viral and bacterial products could affect the response of cells to TNF-α. Incubation of WEHI 164 fibrosarcoma cells with dsRNA or lipopolysaccharide (LPS) significantly increased their sensitivity to TNF-α-mediated lysis and to TNF-secreting inflammatory T cell-mediated lysis. Thus, these products could induce Increased sensitivity to TNF-α In cells In an inflammatory focus, possibly contributing to selective elimination of Infected but not healthy cells by this non-specific cytokine. Additionally, our data show that both dsRNA and LPS, as well as TNF-α Itself, rapidly Induce nuclear factor-xB (NF-*B), a DNA-bindlng protein Implicated In regulation of gene expression. We suggest that NF-xB could regulate genes crucial for the induction of cell death by TNF-α.