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PMID:16244109

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Citation

Dauffy, J, Mouchiroud, G and Bourette, RP (2006) The interferon-inducible gene, Ifi204, is transcriptionally activated in response to M-CSF, and its expression favors macrophage differentiation in myeloid progenitor cells. J. Leukoc. Biol. 79:173-83

Abstract

The interferon-inducible (Ifi)204 gene was isolated as a macrophage-colony stimulating factor (M-CSF)-responsive gene using a gene trap approach in the myeloid interleukin-3 (IL-3)-dependent FD-Fms cell line, which differentiates in macrophages in response to M-CSF. Here, we show that Ifi204 was transcriptionally activated in response to M-CSF, and FD-Fms cells decreased their growth and committed toward a macrophage morphology; this induction was abrogated when the differentiation signal of the M-CSF receptor was blocked; the Ifi204 gene was also induced during macrophage differentiation controlled by leukemia inhibitory factor; and the Ifi204 gene is expressed in different mature monocyte/macrophage cells. Finally, we showed that enforced expression of Ifi204 strongly decreased IL-3- and M-CSF-dependent proliferation and conversely, favored macrophage differentiation of FD-Fms cells in response to M-CSF. Altogether, these results demonstrate that the Ifi204 gene is activated during macrophage development and suggest that the Ifi204 protein may act as a regulator of the balance between proliferation and differentiation. Moreover, this study suggests that other members of the Ifi family might act as regulators of hematopoiesis under the control of hemopoietic cytokines.

Links

PubMed Online version:10.1189/jlb.0205083

Keywords

Animals; Cell Differentiation/drug effects; Cell Differentiation/immunology; Cell Line; Cell Proliferation/drug effects; Gene Expression Regulation/drug effects; Gene Expression Regulation/immunology; Hematopoiesis/genetics; Hematopoiesis/immunology; Humans; Interleukin-3/immunology; Interleukin-3/metabolism; Interleukin-6/immunology; Interleukin-6/metabolism; Leukemia Inhibitory Factor; Macrophage Activation/drug effects; Macrophage Activation/genetics; Macrophage Activation/immunology; Macrophage Colony-Stimulating Factor/immunology; Macrophage Colony-Stimulating Factor/pharmacology; Macrophages/immunology; Macrophages/metabolism; Mice; Myeloid Progenitor Cells/immunology; Myeloid Progenitor Cells/metabolism; Nuclear Proteins/biosynthesis; Nuclear Proteins/genetics; Nuclear Proteins/immunology; Phosphoproteins/biosynthesis; Phosphoproteins/genetics; Phosphoproteins/immunology; Signal Transduction/drug effects; Signal Transduction/genetics; Signal Transduction/immunology; Transcription, Genetic/drug effects; Transcription, Genetic/immunology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:IFI4

GO:0043032: positive regulation of macrophage activation

ECO:0000314:

P

Figure 6C: Analysis of RT-PCR showed that enforced expression of Ifi204 favors M-CSF-dependent macrophage differentiation in in FD-Fms cells.

complete

See also

References

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