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

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

Research output: Contribution to journalArticlepeer-review

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 proliferation in 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 2EE 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. rhIL1 α at a concentration of 10 U/ml inhibited GG2EE proliferation by 25-30%, while rmIFN-γ (25 U/ml) + rhIL1 α (10 U/ml) inhibited proliferation by 98%. Thus, 10 U/ml rhIL1 α could completely replace LPS in the LPS + rmIFN-γ combination. Further, the combination of low doses of rhIL1 α (0.1 to 1 U/ml) plus rmTNF α (250 U/ml), which together inhibited proliferation by 2EE 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.

Original languageEnglish
Pages (from-to)267-276
Number of pages10
JournalBiotherapy
Volume4
Issue number4
DOIs
Publication statusPublished - Dec 1992

Keywords

  • autocrine
  • cytokines
  • immortalized
  • macrophages
  • proliferation

ASJC Scopus subject areas

  • Pharmacology

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