Interleukin-6 activates and regulates transcription factors of the interferon regulatory factor family in M1 cells

• Published in: The Journal of biological chemistry 1993-04, Vol.268 (12), p.9092-9097
• Main Authors: HARROCH, S, GOTHELF, Y, WATANABE, N, REVEL, M, CHEBATH, J
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; Binding Sites; Biological and medical sciences; Blotting, Northern; Cell Line; Cell physiology; CHO Cells; Cricetinae; DNA; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Enhancer Elements, Genetic; Fundamental and applied biological sciences. Psychology; Humans; Interferon Regulatory Factor-1; Interferon Regulatory Factor-2; Interleukin-6 - physiology; Kinetics; Mice; Molecular and cellular biology; Molecular Sequence Data; Phosphoproteins - genetics; Phosphoproteins - metabolism; Repressor Proteins; Responses to growth factors, tumor promotors, other factors; RNA, Messenger - metabolism; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)52981-1

Activation of (2'-5') A synthetase gene expression in interleukin-6 (IL-6)-treated myeloleukemic M1 cells correlates with protein binding to the interferon response sequence enhancer (IRS). A new interferon response sequence complex, F6, is induced by IL-6 independently of interferon and is identified here as comprising the interferon regulatory factor-1 (IRF-1) and IRF-2, by use of specific antibodies in DNA mobility shift assays with probes containing IRF binding sites. IRF-1 and IRF-2 have, respectively, positive and negative transcriptional effects on interferon-beta and interferon-inducible genes. In the IL-6-treated M1or cells, IRF-1 binding is activated early and maximally at 1 h, whereas the onset of IRF-2 binding is delayed. In a cell variant M1res, where (2'-5') A synthetase is no more induced, IRF-2 binding is constitutive, and IRF-1 binding is not seen before or after IL-6 treatment. In sensitive M1or cells, IL-6 rapidly induces IRF-1 mRNA, but in M1res cells, IRF-1 mRNA is constitutively high and not changed by IL-6. IRF-2 mRNA levels are also constitutive and not inducible by IL-6 even in M1or cells. The dissociation between induction of mRNAs and of protein binding observed suggests that the activity of the IRF proteins is regulated by IL-6. Transcripts of a third member of the IRF gene family, ICSBP, encoding a protein known to act as repressor, were found to be strongly down-regulated by IL-6. The rapid activation of IRF-1 and the modulation of the other transcription factors of this family may play a role in the early phase of IL-6 action on the M1 cells.