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Continuous interferon-gamma inhibits interleukin-3-dependent gene expression and cell proliferation of human myeloid cells.
The present study was undertaken to examine the effect of interferon-gamma (IFN-gamma) on the expression of the proto-oncogene c-myc and of the interleukin 3 (IL-3)-responsive gene transferrin receptor (TfR). To this aim, we have used the line THP-1 and its differentiation to macrophages and granulocytes induced by interferon-gamma, and have compared it with the erythroleukemic line HEL. The results showed that IFN-gamma (1-1000 U/ml) induced an additive inhibitory effect of IL-3-dependent growth and c-myc and TfR transcription of THP-1 cells. By contrast, HEL cells responded to IFN-gamma (1-1000 U/ml) with a dose-dependent inhibition of IL-3-dependent cell growth. In both cell lines, the effect of IFN-gamma (500 U/ml) on c-myc and TfR mRNA levels could be mimicked by an addition of IL-3 (10 U/ml) after a short-time incubation with IFN-gamma (500 U/ml). IFN-gamma (500 U/ml) can directly inhibit the proliferation of both THP-1 and HEL cells as assessed by the incorporation of [3H]thymidine. However, the addition of IL-3 to THP-1 cells cultured for 24 h in the presence of IFN-gamma (500 U/ml) showed a transient increase in the TfR mRNA level which was paralleled by a transient increase in cell-surface TfR. On the contrary, HEL cells cultured for 48 h in the presence of IFN-gamma (500 U/ml) did not show such an increase. The possible relationship between IFN-gamma effects on the proliferation of myeloid cells and on c-myc expression is discussed.Follow Us

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