Interleukin-6 induces the (2'-5') oligoadenylate synthetase gene in M1 cells through an effect on the interferon-responsive enhancer.
Interleukin-6 (IL-6) activates (2'-5') A synthetase (2'-5' AS) gene expression in differentiating myeloleukemic M1 cells. Antibodies to type I interferon (IFN) inhibit 2'-5' AS induction but not differentiation. Analysis of the mechanism of 2'-5' AS induction shows that it does not result from increased IFN formation, but from a synergism between IL-6 and endogenously secreted IFN. IL-6 can activate expression of a CAT construct fused to the interferon response sequence (IRS) of the 2'-5' AS gene. In extracts of IL-6-treated M1 cells, changes in protein binding to IRS DNA can be demonstrated. One of the effects of IL-6 on M1 cells is, therefore, to induce DNA binding factors, some of which act on the same enhancer sequence as IFNs, resulting in a synergistic gene activation. M1 variants resistant to differentiation by IL-6 have lost the ability to induce the 2'-5' AS gene.
Cohen
B
B
Department of Molecular Genetics and Virology, Weizmann Institute of Science, Rehovot, Israel.
Gothelf
Y
Y
Vaiman
D
D
Chen
L
L
Revel
M
M
Chebath
J
J
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D004790:Enzyme Induction; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D007370:Interferon Type I / Q000276:immunology / Q000502:physiology*; D015850:Interleukin-6 / Q000494:pharmacology*; D007942:Leukemia, Experimental; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011994:Recombinant Proteins / Q000494:pharmacology*; D015533:Transcriptional Activation; D014162:Transfection
D000906:Antibodies; D004273:DNA, Neoplasm; D007370:Interferon Type I; D015850:Interleukin-6; D015345:Oligonucleotide Probes; D011994:Recombinant Proteins; D015088:2',5'-Oligoadenylate Synthetase