Macrophage differentiation-specific expression of NF-IL6, a transcription factor for interleukin-6.
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.
Natsuka
S
S
Institute for Molecular and Cellular Biology, Osaka University, Japan.
Akira
S
S
Nishio
Y
Y
Hashimoto
S
S
Sugita
T
T
Isshiki
H
H
Kishimoto
T
T
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D015153:Blotting, Western; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000494:pharmacology; D007948:Leukemia, Monocytic, Acute; D008264:Macrophages / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D015850:Interleukin-6; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014157:Transcription Factors; D004247:DNA