Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6

Abstract

NF-IL6 was originally identified as a DNA binding protein regulating interleukin-1 (IL-1)-stimulated IL-6 expression. Direct cloning of NF- IL6 showed its homology with C/EBP, a hepatocyte- and adipocyte- specific transcription factor. This study showed that the expression of NF-IL6 messenger RNA (mRNA) increased markedly during the differentiation to a (mRNA) increased markedly during the differentiation to a macrophage lineage in mouse myeloid leukemia cells M1, human histiocytic leukemia cells U937, promyelocytic leukemia cells HL-60, and human peripheral monocytes. Particularly in HL-60 cells that undergo granulocyte or macrophage differentiation depending on inducers, NF-IL6 mRNA was specifically upregulated during macrophage differentiation but not granulocyte differentiation. It was also shown that the functional NF-IL6 protein increased during the differentiation of U937 cells. Furthermore, recombinant NF-IL6 was found to bind to the regulatory regions of the IL-1, tumor necrosis factor, granulocyte colony-stimulating factor, and lysozyme genes, which are expressed in mature macrophages. These results suggest that NF-IL6 may possibly be involved as an important transcription factor in the process of activation and/or differentiation of macrophages.

NF-M (chicken C/EBP beta) induces eosinophilic differentiation and apoptosis in a hematopoietic progenitor cell line.

“…Another tissue in which C/EBP-type factors play a role is the hematopoietic system. As observed for adipocyte maturation, myelomonocytic differentiation is paralleled by a distinct expression pattern of C/EBP proteins which, however, is different from that in adipocytes (Cao et al, 1991;Natsuka et al, 1992;Scott et al, 1992). Thus, C/EBP, has been shown to be expressed and active in macrophages during the inflammatory reaction and acute phase response (Akira et al, 1990;Poli et al, 1990;Akira and Kishimoto, 1992;Juan et al, 1993;Katz et al, 1993;Ramji et al, 1993;Pope et al, 1994).…”

Signal Transduction in the Liver: C/Ebpβ Modulates Cell Proliferation and Survival

“…53 The proposed role of C/EBP␤ (and phosphorylated C/EBP␤) on the modulation of hepatocyte quiescence/ proliferation is supported by the effects of C/EBP␤ on differentiation and cell arrest/proliferation of myelomonocytes, eosinophils, macrophages, B lymphocytes, and adipocytes. 49,[54][55][56] A dual repressive/activation function of unphosphorylated/phosphorylated C/EBP␤ on the hepatocyte cell cycle has been proposed. 9 This hypothesis is supported by the finding that C/EBP␤ is a repressed transcription factor with a concealed activation potential that becomes unmasked by kinase oncogenes.…”

A Novel Glycogen Synthase Kinase-3 Inhibitor Optimized for Acute Myeloid Leukemia Differentiation Activity

“…5A). CEBPb is a key regulator in myeloid differentiation (36,37), whereas cyclin D2 has roles in leukemia proliferation (38)(39)(40). IRF8 is a regulator of myeloid differentiation and high expression has been linked to poor prognosis in AML (41).…”