Early growth response transcriptional regulators are dispensable for macrophage differentiation

被引:48
作者
Carter, John H.
Tourtellotte, Warren G.
机构
[1] Northwestern Univ, Dept Pathol, Chicago, IL 60611 USA
[2] Northwestern Univ, Div Neuropathol, Chicago, IL 60611 USA
[3] Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA
关键词
D O I
10.4049/jimmunol.178.5.3038
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Early growth response (Egr) proteins comprise a family of transcriptional regulators (Egrl-4) that modulate gene expression involved in the growth and differentiation of many cell types. In particular, Egr1 is widely believed to have an essential role in regulating monocyte/macrophage differentiation. However, Egr1-deficient mice have normal numbers of functional macrophages, an observation that has led to the hypothesis that other Egr proteins may compensate for Egr1 function in vivo. We examined whether other Egr transcription factors have a functionally redundant role in monocyte/macrophage differentiation. Egr1 and Egr3 expression was found to be induced in myeloid cells when they were differentiated into macrophages by treatment with M-CSF, whereas Egr2 was minimally induced and Egr4 was not detected. In either Egr1/Egr3 or Egrl/ Egr2 double homozygous mutant mice, macrophage differentiation and function remained unimpaired. Additionally, the expression of molecules that broadly inhibit Egr function failed to block commitment to the monocytic lineage or inhibit the maturation of monocyte precursors. Finally, several hemopoietic growth factors were found to induce Egr gene expression, indicating that Egr gene expression is not cell lineage specific. Taken together, these results demonstrate that Egr transcription factors are neither essential for nor specific to monocyte/macrophage differentiation.
引用
收藏
页码:3038 / 3047
页数:10
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