Gamma interferon induces expression of Mad1 gene in mocrophage, which inhibits colony-stimulating factor-1-dependent mitogenesis

Arunangsu Dey, Leopold Kim, Wei Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Gamma interferon (IFNγ) has long been known as an antiproliferative cytokine. The mechanism of its action, however, remains elusive. Monocytes and macrophages are primary targets of IFNγ. To understand the antiproliferative signaling of IFNγ, we studied the effect of IFNγ on expression of c-Myc, Mad1, Max, cyclin D1, and cyclin D2 genes in both a macrophage cell line and in primary bone marrow-derived macrophages (BMM) in response to colony-stimulating factor-1 (CSF-1). We found that whereas IFNγ inhibits CSF-1-stimulated c-Myc gene expression, it induced Mad1 expression. Induction of Mad1 mRNA could be detected as early as 90 min following IFNγ)treatment and was maintained for at least 15 h. These results suggest that IFNγ treatment could shift the Myc-Max complex to the Mad1-Max complex in cells. The levels of Max, cyclin D1, and cyclin D2, however, remained unchanged. Enforced ectopic expression of Mad1 in the cells results inhibition of [ 3 H]tymidine incorporation and proliferation in response to CSF-1. This study suggests a mechanism by which IFNγ inhibits CSF-1- stimulated proliferation of macrophages, i.e., by elevating the Mad1 level in the cells.

Original languageEnglish (US)
Pages (from-to)232-241
Number of pages10
JournalJournal of Cellular Biochemistry
Volume72
Issue number2
DOIs
StatePublished - Jan 15 1999

Keywords

  • Antiproliferation
  • Cytokine
  • Growth factor
  • Oncogene
  • Signal transduction
  • Tumor suppressor gene

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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