Recombinant human tumor necrosis factor and recombinant human γ interferon (IFN-γ) exert synergistic growth inhibitory effects in WiDR human colorectal carcinoma cells. In this cell line, tumor necrosis factor increases IFN-γ binding. Interleukin 1 (IL-1) is a cytokine that mimics many of the biological actions of TNF. Therefore, in the present study, we investigated the effects of recombinant human IL-1 on cell growth and IFN-γ receptor expression in WiDR cells. IL-1 slightly inhibited the growth of WiDR cells, and exerted additive growth inhibitory effects in the presence of IFN-γ. IL-1 caused a time- and dose-dependent increase in 125I-labeled IFN-γ binding that was maximal at 6 h, persisted for at least 24 h, and was blocked by both actinomycin D and cycloheximide. The increase in binding was associated with an increase in cell surface IFN-γ receptor protein expression as determined by Scatchard analysis of equilibrium binding data and by immunofluorescent staining with an anti-human IFN-γ receptor monoclonal antibody. IL-1 also produced a time- and dose-dependent increase in IFN-γ receptor mRNA levels that was maximal at 3 h and persisted for at least 24 h. Actinomycin D, but not cycloheximide, completely blocked the IL-1-mediated increase in IFN-γ receptor mRNA levels. However, IL-1 did not alter IFN-γ receptor mRNA half-life. These data indicate that IL-1 and IFN-γ exert additive growth inhibitory effects on colon cancer cell growth, and suggest that IL-1 increases IFN-γ receptor expression in these cells by enhancing IFN-γ mRNA levels.
This investigation was supported by USPHA Grant CA-40162, awarded from the National Cancer Institute, Department of Health and Human Services.