Growth inhibition of a human colorectal carcinoma cell line by interleukin 1 is associated with enhanced expression of gamma-interferon receptors.
Recombinant human tumor necrosis factor and recombinant human gamma interferon (IFN-gamma) exert synergistic growth inhibitory effects in WiDR human colorectal carcinoma cells. In this cell line, tumor necrosis factor increases IFN-gamma 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-gamma 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-gamma. IL-1 caused a time- and dose-dependent increase in 125I-labeled IFN-gamma 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-gamma receptor protein expression as determined by Scatchard analysis of equilibrium binding data and by immunofluorescent staining with an anti-human IFN-gamma receptor monoclonal antibody. IL-1 also produced a time- and dose-dependent increase in IFN-gamma 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-gamma receptor mRNA levels. However, IL-1 did not alter IFN-gamma receptor mRNA half-life. These data indicate that IL-1 and IFN-gamma exert additive growth inhibitory effects on colon cancer cell growth, and suggest that IL-1 increases IFN-gamma receptor expression in these cells by enhancing IFN-gamma mRNA levels.
Raitano
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Department of Medicine, University of California, Irvine 92717.
Korc
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D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000648:ultrastructure; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D007457:Iodine Radioisotopes; D007700:Kinetics; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis; D017471:Receptors, Interferon / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D007375:Interleukin-1; D007457:Iodine Radioisotopes; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor