C/EBPε is a myeloid-specific activator of cytokine, chemokine, and macrophage-colony-stimulating factor receptor genes

Abstract

C/EBPε is a member of the CCAAT/enhancer binding protein family of basic region/leucine zipper transcriptional activators. The C/EBPε protein is highly conserved between rodents and humans, and its domain structure is very similar to C/EBPα. In mice C/EBPε mRNA is only detected in hematopoietic tissues, including embryonic liver and adult bone marrow and spleen. Within the hematopoietic system, C/EBPε is expressed primarily in myeloid cells, including promyelocytes, myelomonocytes, and their differentiated progeny. To identify potential functions of C/EBPε, cell lines overexpressing the C/EBPε protein were generated in the P388 lymphoblastic cell line. In contrast to the parental cell line, C/EBPε- expressing cell lines displayed lipopolysaccharide-inducible expression of the interleukin-6 and monocyte chemoattractant protein 1 (MCP-1) genes as well as elevated basal expression of the MIP-1α and MIP-1β chemokine genes. In the EML-C1 hematopoietic stem cell line, C/EBPε mRNA levels increased as the cells progressed along the myeloid lineage, just preceding activation of the gene encoding the receptor for macrophage-colony-stimulating factor (M- CSFR). M-CSFR expression was stimulated in C/EBPε-expressing P388 cell lines, when compared with either the parental P388 cells or P388 cell lines expressing either C/EBPα or C/EBPβ. These results suggest that C/EBPε may be an important regulator of differentiation of a subset of myeloid cell types and may also participate in the regulation of cytokine gene expression in mature cells.