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Inhibition of proliferation of retrovirus-immortalized macrophages by LPS and IFN-γ: Possible autocrine down-regulation of cell growth by induction of IL1 and TNF

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Biotherapy

Abstract

The GG2EE macrophage tumor cell line was previously established by immortalization of C3H/HeJ mouse bone marrow cells with the J2 retrovirus which contains the v-myc and v-raf oncogenes. Studies on the control of GGZEE cell proliferationin vitro have recently been performed. We observed that the combination of 5–25 U/ml recombinant mouse interferon-γ (rmIFN-γ) plus 0.03 – 0.3 µg/ml lipopolysaccharide (LPS) markedly inhibited the proliferation of GG2EE cells (by >95%)in vitro, while either agent alone inhibited only by <40% and 0–10%, respectively. Subsequent studies established that biologically active ILI-like (2–4 U/ml) and TNFα-like (50–100 U/ml) activities were released into the supernatants of LPS-treated GG2EE cells. The combination of IFN-γ + LPS induced more (6–8 U/ml) ILI release. These results suggested that the inhibition of proliferation of GG2EE cells by IFN-γ + LPS could have been mediated in part by cytokines produced by the cells themselves. rhIL1α at a concentration of 10 U/ml inhibited GG2EE proliferation by 25–30%, while rmIFN-γ (25 U/ml) + rhIL1α (10 U/ml) inhibited proliferation by 98%. Thus, 10 U/ml rhIL1α could completely replace LPS in the LPS + rmIFN-γ combination. Further, the combination of low doses of rhIL1α (0.1 to 1 U/ml) plus rmTNFα (250 U/ml), which together inhibited proliferation by <20% synergized with doses of 5 to 25 U/ml rmIFN-γ to inhibit proliferation of GG2EE cells by 98–99%. These results suggest that cytokines produced by the cells themselves can synergize with rmIFN-γ to inhibit the oncogene-driven proliferation of GG2EE cells.

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  1. Emira Ayroldi

    Present address: Institute of Pharmacology, University of Perugia, Perugia, Italy

Authors and Affiliations

  1. Laboratory of Experimental Immunology and Laboratory of Molecular Immunoregulation, Biological Response Modifiers Program, National Cancer Institute, Frederick Cancer Research and Development Center, 21702-1201, Frederick, Maryland

    Emira Ayroldi, Elisabetta Blasi, Luigi Varesio & Robert H. Wiltrout

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  1. Emira Ayroldi
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  2. Elisabetta Blasi
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  3. Luigi Varesio
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  4. Robert H. Wiltrout
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Ayroldi, E., Blasi, E., Varesio, L. et al. Inhibition of proliferation of retrovirus-immortalized macrophages by LPS and IFN-γ: Possible autocrine down-regulation of cell growth by induction of IL1 and TNF. Biotherapy 4, 267–276 (1992). https://doi.org/10.1007/BF02172656

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  • DOI: https://doi.org/10.1007/BF02172656

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