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. 1989 Dec;86(24):9936–9940. doi: 10.1073/pnas.86.24.9936

Induction of the transcription factor IRF-1 and interferon-beta mRNAs by cytokines and activators of second-messenger pathways.

T Fujita 1, L F Reis 1, N Watanabe 1, Y Kimura 1, T Taniguchi 1, J Vilcek 1
PMCID: PMC298617  PMID: 2557635

Abstract

Nuclear protein IRF-1 (interferon regulatory factor 1) was earlier shown to bind to cis-acting regulatory elements present on interferon (IFN)-alpha/beta genes and some IFN-inducible genes. Here we show that in both human FS-4 and murine L929 cells, steady-state levels of IRF-1 mRNA were increased by treatment with tumor necrosis factor (TNF), interleukin 1 (IL-1), poly(I).poly(C), or IFN-beta. IRF-1 mRNA induction was also demonstrated in cells treated with calcium ionophore A23187 or with phorbol 12-myristate 13-acetate, but not with epidermal growth factor, dibutyryl-cAMP, or the adenylate cyclase activator forskolin. To determine whether stimulation of IRF-1 mRNA levels correlates with IFN-beta induction, we compared IRF-1 and IFN-beta mRNA levels in cells exposed to various stimuli. In L929 cells, treatment with poly(I).poly(C) under conditions that failed to induce significant levels of IFN-beta mRNA led to a very low induction of IRF-1 mRNA, but "priming" cells with IFN prior to the addition of poly(I).poly(C) greatly increased both IRF-1 and IFN-beta mRNAs. In FS-4 cells an increase in IFN-beta mRNA (examined by the polymerase chain reaction) was seen after treatment with TNF, IL-1, A23187, or poly(I).poly(C), but not with IFN-beta, epidermal growth factor, dibutyryl-cAMP, or forskolin. Thus, all treatments that increased steady-state levels of IFN-beta mRNA also enhanced IRF-1 mRNA levels. However, treatment with IFN-beta, which caused a marked stimulation in IRF-1 mRNA, failed to produce a detectable increase in IFN-beta mRNA. It appears that IRF-1 may be necessary but not sufficient for IFN-beta induction. The ability of TNF and IL-1 to increase both IRF-1 and IFN-beta mRNAs may be responsible for some similarities in the actions of TNF, IL-1, and the IFNs.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Babich A., Feldman L. T., Nevins J. R., Darnell J. E., Jr, Weinberger C. Effect of adenovirus on metabolism of specific host mRNAs: transport control and specific translational discrimination. Mol Cell Biol. 1983 Jul;3(7):1212–1221. doi: 10.1128/mcb.3.7.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beresini M. H., Lempert M. J., Epstein L. B. Overlapping polypeptide induction in human fibroblasts in response to treatment with interferon-alpha, interferon-gamma, interleukin 1 alpha, interleukin 1 beta, and tumor necrosis factor. J Immunol. 1988 Jan 15;140(2):485–493. [PubMed] [Google Scholar]
  3. Clark L., Hay R. T. Sequence requirement for specific interaction of an enhancer binding protein (EBP1) with DNA. Nucleic Acids Res. 1989 Jan 25;17(2):499–516. doi: 10.1093/nar/17.2.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Collins T., Lapierre L. A., Fiers W., Strominger J. L., Pober J. S. Recombinant human tumor necrosis factor increases mRNA levels and surface expression of HLA-A,B antigens in vascular endothelial cells and dermal fibroblasts in vitro. Proc Natl Acad Sci U S A. 1986 Jan;83(2):446–450. doi: 10.1073/pnas.83.2.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Derynck R., Content J., DeClercq E., Volckaert G., Tavernier J., Devos R., Fiers W. Isolation and structure of a human fibroblast interferon gene. Nature. 1980 Jun 19;285(5766):542–547. doi: 10.1038/285542a0. [DOI] [PubMed] [Google Scholar]
  6. Fujita T., Kimura Y., Miyamoto M., Barsoumian E. L., Taniguchi T. Induction of endogenous IFN-alpha and IFN-beta genes by a regulatory transcription factor, IRF-1. Nature. 1989 Jan 19;337(6204):270–272. doi: 10.1038/337270a0. [DOI] [PubMed] [Google Scholar]
  7. Fujita T., Kohno S. Studies on interferon priming: cellular response to viral and nonviral inducers and requirement of protein synthesis. Virology. 1981 Jul 15;112(1):62–69. doi: 10.1016/0042-6822(81)90612-7. [DOI] [PubMed] [Google Scholar]
  8. Fujita T., Miyamoto M., Kimura Y., Hammer J., Taniguchi T. Involvement of a cis-element that binds an H2TF-1/NF kappa B like factor(s) in the virus-induced interferon-beta gene expression. Nucleic Acids Res. 1989 May 11;17(9):3335–3346. doi: 10.1093/nar/17.9.3335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fujita T., Sakakibara J., Sudo Y., Miyamoto M., Kimura Y., Taniguchi T. Evidence for a nuclear factor(s), IRF-1, mediating induction and silencing properties to human IFN-beta gene regulatory elements. EMBO J. 1988 Nov;7(11):3397–3405. doi: 10.1002/j.1460-2075.1988.tb03213.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Fujita T., Shibuya H., Hotta H., Yamanishi K., Taniguchi T. Interferon-beta gene regulation: tandemly repeated sequences of a synthetic 6 bp oligomer function as a virus-inducible enhancer. Cell. 1987 May 8;49(3):357–367. doi: 10.1016/0092-8674(87)90288-1. [DOI] [PubMed] [Google Scholar]
  11. Garcia-Blanco M. A., Lengyel P., Morrison E., Brownlee C., Stiles C. D., Rutherford M., Hannigan G., Williams B. R. Regulation of 2',5'-oligoadenylate synthetase gene expression by interferons and platelet-derived growth factor. Mol Cell Biol. 1989 Mar;9(3):1060–1068. doi: 10.1128/mcb.9.3.1060. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Goodbourn S., Maniatis T. Overlapping positive and negative regulatory domains of the human beta-interferon gene. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1447–1451. doi: 10.1073/pnas.85.5.1447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Griffin G. E., Leung K., Folks T. M., Kunkel S., Nabel G. J. Activation of HIV gene expression during monocyte differentiation by induction of NF-kappa B. Nature. 1989 May 4;339(6219):70–73. doi: 10.1038/339070a0. [DOI] [PubMed] [Google Scholar]
  14. Harada H., Fujita T., Miyamoto M., Kimura Y., Maruyama M., Furia A., Miyata T., Taniguchi T. Structurally similar but functionally distinct factors, IRF-1 and IRF-2, bind to the same regulatory elements of IFN and IFN-inducible genes. Cell. 1989 Aug 25;58(4):729–739. doi: 10.1016/0092-8674(89)90107-4. [DOI] [PubMed] [Google Scholar]
  15. Hirai M., Okamura N., Terano Y., Tsujimoto M., Nakazato H. Production and characterization of monoclonal antibodies to human tumor necrosis factor. J Immunol Methods. 1987 Jan 26;96(1):57–62. doi: 10.1016/0022-1759(87)90367-x. [DOI] [PubMed] [Google Scholar]
  16. Hug H., Costas M., Staeheli P., Aebi M., Weissmann C. Organization of the murine Mx gene and characterization of its interferon- and virus-inducible promoter. Mol Cell Biol. 1988 Aug;8(8):3065–3079. doi: 10.1128/mcb.8.8.3065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Keller A. D., Maniatis T. Identification of an inducible factor that binds to a positive regulatory element of the human beta-interferon gene. Proc Natl Acad Sci U S A. 1988 May;85(10):3309–3313. doi: 10.1073/pnas.85.10.3309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kohase M., May L. T., Tamm I., Vilcek J., Sehgal P. B. A cytokine network in human diploid fibroblasts: interactions of beta-interferons, tumor necrosis factor, platelet-derived growth factor, and interleukin-1. Mol Cell Biol. 1987 Jan;7(1):273–280. doi: 10.1128/mcb.7.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kohase M., Zhang Y. H., Lin J. X., Yamazaki S., Sehgal P. B., Vilcek J. Interleukin-1 can inhibit interferon-beta synthesis and its antiviral action: comparison with tumor necrosis factor. J Interferon Res. 1988 Aug;8(4):559–570. doi: 10.1089/jir.1988.8.559. [DOI] [PubMed] [Google Scholar]
  20. Kuhl D., de la Fuente J., Chaturvedi M., Parimoo S., Ryals J., Meyer F., Weissmann C. Reversible silencing of enhancers by sequences derived from the human IFN-alpha promoter. Cell. 1987 Sep 25;50(7):1057–1069. doi: 10.1016/0092-8674(87)90172-3. [DOI] [PubMed] [Google Scholar]
  21. Lenardo M. J., Fan C. M., Maniatis T., Baltimore D. The involvement of NF-kappa B in beta-interferon gene regulation reveals its role as widely inducible mediator of signal transduction. Cell. 1989 Apr 21;57(2):287–294. doi: 10.1016/0092-8674(89)90966-5. [DOI] [PubMed] [Google Scholar]
  22. Levy D. E., Kessler D. S., Pine R., Reich N., Darnell J. E., Jr Interferon-induced nuclear factors that bind a shared promoter element correlate with positive and negative transcriptional control. Genes Dev. 1988 Apr;2(4):383–393. doi: 10.1101/gad.2.4.383. [DOI] [PubMed] [Google Scholar]
  23. Lowenthal J. W., Ballard D. W., Böhnlein E., Greene W. C. Tumor necrosis factor alpha induces proteins that bind specifically to kappa B-like enhancer elements and regulate interleukin 2 receptor alpha-chain gene expression in primary human T lymphocytes. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2331–2335. doi: 10.1073/pnas.86.7.2331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Maruyama M., Fujita T., Taniguchi T. Sequence of a cDNA coding for human IRF-1. Nucleic Acids Res. 1989 Apr 25;17(8):3292–3292. doi: 10.1093/nar/17.8.3292. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Mestan J., Digel W., Mittnacht S., Hillen H., Blohm D., Möller A., Jacobsen H., Kirchner H. Antiviral effects of recombinant tumour necrosis factor in vitro. 1986 Oct 30-Nov 5Nature. 323(6091):816–819. doi: 10.1038/323816a0. [DOI] [PubMed] [Google Scholar]
  26. Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi: 10.1016/s0092-8674(88)91307-4. [DOI] [PubMed] [Google Scholar]
  27. Onozaki K., Urawa H., Tamatani T., Iwamura Y., Hashimoto T., Baba T., Suzuki H., Yamada M., Yamamoto S., Oppenheim J. J. Synergistic interactions of interleukin 1, interferon-beta, and tumor necrosis factor in terminally differentiating a mouse myeloid leukemic cell line (M1). Evidence that interferon-beta is an autocrine differentiating factor. J Immunol. 1988 Jan 1;140(1):112–119. [PubMed] [Google Scholar]
  28. Pfizenmaier K., Scheurich P., Schlüter C., Krönke M. Tumor necrosis factor enhances HLA-A,B,C and HLA-DR gene expression in human tumor cells. J Immunol. 1987 Feb 1;138(3):975–980. [PubMed] [Google Scholar]
  29. Reis L. F., Ho Lee T., Vilcek J. Tumor necrosis factor acts synergistically with autocrine interferon-beta and increases interferon-beta mRNA levels in human fibroblasts. J Biol Chem. 1989 Oct 5;264(28):16351–16354. [PubMed] [Google Scholar]
  30. Rubin B. Y., Anderson S. L., Lunn R. M., Richardson N. K., Hellermann G. R., Smith L. J., Old L. J. Tumor necrosis factor and IFN induce a common set of proteins. J Immunol. 1988 Aug 15;141(4):1180–1184. [PubMed] [Google Scholar]
  31. Ryals J., Dierks P., Ragg H., Weissmann C. A 46-nucleotide promoter segment from an IFN-alpha gene renders an unrelated promoter inducible by virus. Cell. 1985 Jun;41(2):497–507. doi: 10.1016/s0092-8674(85)80023-4. [DOI] [PubMed] [Google Scholar]
  32. Taniguchi T. Regulation of cytokine gene expression. Annu Rev Immunol. 1988;6:439–464. doi: 10.1146/annurev.iy.06.040188.002255. [DOI] [PubMed] [Google Scholar]
  33. Tiwari R. K., Kusari J., Sen G. C. Functional equivalents of interferon-mediated signals needed for induction of an mRNA can be generated by double-stranded RNA and growth factors. EMBO J. 1987 Nov;6(11):3373–3378. doi: 10.1002/j.1460-2075.1987.tb02659.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Van Damme J., Opdenakker G., Billiau A., De Somer P., De Wit L., Poupart P., Content J. Stimulation of fibroblast interferon production by a 22K protein from human leukocytes. J Gen Virol. 1985 Apr;66(Pt 4):693–700. doi: 10.1099/0022-1317-66-4-693. [DOI] [PubMed] [Google Scholar]
  35. Vilcek J., Havell E. A. Stabilization of interferon messenger RNA activity by treatment of cells with metabolic inhibitors and lowering of the incubation temperature. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3909–3913. doi: 10.1073/pnas.70.12.3909. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Visvanathan K. V., Goodbourn S. Double-stranded RNA activates binding of NF-kappa B to an inducible element in the human beta-interferon promoter. EMBO J. 1989 Apr;8(4):1129–1138. doi: 10.1002/j.1460-2075.1989.tb03483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Wathelet M. G., Clauss I. M., Nols C. B., Content J., Huez G. A. New inducers revealed by the promoter sequence analysis of two interferon-activated human genes. Eur J Biochem. 1987 Dec 1;169(2):313–321. doi: 10.1111/j.1432-1033.1987.tb13614.x. [DOI] [PubMed] [Google Scholar]
  38. Zinn K., Maniatis T. Detection of factors that interact with the human beta-interferon regulatory region in vivo by DNAase I footprinting. Cell. 1986 May 23;45(4):611–618. doi: 10.1016/0092-8674(86)90293-x. [DOI] [PubMed] [Google Scholar]
  39. Zullo J. N., Cochran B. H., Huang A. S., Stiles C. D. Platelet-derived growth factor and double-stranded ribonucleic acids stimulate expression of the same genes in 3T3 cells. Cell. 1985 Dec;43(3 Pt 2):793–800. doi: 10.1016/0092-8674(85)90252-1. [DOI] [PubMed] [Google Scholar]

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