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Gamma interferon induces expression of Mad1 gene in macrophage, which inhibits colony‐stimulating factor‐1–dependent mitogenesis
Author(s) -
Dey Arunangsu,
Kim Leopold,
Li Wei
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19990201)72:2<232::aid-jcb7>3.0.co;2-0
Subject(s) - macrophage , biology , microbiology and biotechnology , gene , interferon gamma , gene expression , interferon , macrophage colony stimulating factor , cancer research , cytokine , immunology , genetics , in vitro
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 induces 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 in inhibition of [ 3 H]thymidine 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. J. Cell. Biochem. 72:232–241, 1999. © 1999 Wiley‐Liss, Inc.