Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1989 Mar;86(5):1490–1494. doi: 10.1073/pnas.86.5.1490

Coordinate viral induction of tumor necrosis factor alpha and interferon beta in human B cells and monocytes.

A E Goldfeld 1, T Maniatis 1
PMCID: PMC286722  PMID: 2537976

Abstract

Human tumor necrosis factor alpha (TNF-alpha) gene expression can be induced primarily in cells of the monocyte/macrophage lineage by a variety of inducers, including lipopolysaccharide, phorbol esters such as phorbol 12-myristate 13-acetate, and virus or synthetic double-stranded RNA [poly(I).poly(C)]. In this paper we show that the TNF-alpha gene also responds to virus and phorbol 12-myristate 13-acetate in B lymphocytes and that virus is the most potent inducer of TNF-alpha mRNA in both monocyte and B-cell lines. In addition, we show that viral infection coinduces the expression of TNF-alpha and interferon beta mRNA and that viral induction of both genes is blocked by the kinase inhibitor 2-aminopurine. Inhibition of protein synthesis with cycloheximide had no effect on mRNA expression of the genes in one of three cell lines tested (U937) but blocked the viral induction of both genes in another (Namalwa). Thus, the regulatory factors required for mRNA induction of both genes are present prior to the addition of virus in U937 but not in Namalwa cells. However, in a third cell line (JY), cycloheximide blocked viral induction of the interferon beta gene but not the TNF-alpha gene. Taken together, these observations suggest that viral induction of TNF-alpha and interferon beta gene expression may involve overlapping pathways with both common and distinct regulatory factors.

Full text

PDF
1490

Images in this article

1491Image
on p.1491
1491Image
on p.1491
1492Image
on p.1492
1493Image
on p.1493

Selected References

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

  1. Aderka D., Holtmann H., Toker L., Hahn T., Wallach D. Tumor necrosis factor induction by Sendai virus. J Immunol. 1986 Apr 15;136(8):2938–2942. [PubMed] [Google Scholar]
  2. Berent S. L., Torczynski R. M., Bollon A. P. Sendai virus induces high levels of tumor necrosis factor mRNA in human peripheral blood leukocytes. Nucleic Acids Res. 1986 Nov 25;14(22):8997–9015. doi: 10.1093/nar/14.22.8997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beutler B., Cerami A. Cachectin and tumour necrosis factor as two sides of the same biological coin. Nature. 1986 Apr 17;320(6063):584–588. doi: 10.1038/320584a0. [DOI] [PubMed] [Google Scholar]
  4. Beutler B., Krochin N., Milsark I. W., Luedke C., Cerami A. Control of cachectin (tumor necrosis factor) synthesis: mechanisms of endotoxin resistance. Science. 1986 May 23;232(4753):977–980. doi: 10.1126/science.3754653. [DOI] [PubMed] [Google Scholar]
  5. Bevilacqua M. P., Pober J. S., Majeau G. R., Fiers W., Cotran R. S., Gimbrone M. A., Jr Recombinant tumor necrosis factor induces procoagulant activity in cultured human vascular endothelium: characterization and comparison with the actions of interleukin 1. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4533–4537. doi: 10.1073/pnas.83.12.4533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bevilacqua M. P., Pober J. S., Mendrick D. L., Cotran R. S., Gimbrone M. A., Jr Identification of an inducible endothelial-leukocyte adhesion molecule. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9238–9242. doi: 10.1073/pnas.84.24.9238. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Broudy V. C., Kaushansky K., Segal G. M., Harlan J. M., Adamson J. W. Tumor necrosis factor type alpha stimulates human endothelial cells to produce granulocyte/macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7467–7471. doi: 10.1073/pnas.83.19.7467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carswell E. A., Old L. J., Kassel R. L., Green S., Fiore N., Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. doi: 10.1073/pnas.72.9.3666. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Enoch T., Zinn K., Maniatis T. Activation of the human beta-interferon gene requires an interferon-inducible factor. Mol Cell Biol. 1986 Mar;6(3):801–810. doi: 10.1128/mcb.6.3.801. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Farrell P. J., Balkow K., Hunt T., Jackson R. J., Trachsel H. Phosphorylation of initiation factor elF-2 and the control of reticulocyte protein synthesis. Cell. 1977 May;11(1):187–200. doi: 10.1016/0092-8674(77)90330-0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Goeddel D. V., Aggarwal B. B., Gray P. W., Leung D. W., Nedwin G. E., Palladino M. A., Patton J. S., Pennica D., Shepard H. M., Sugarman B. J. Tumor necrosis factors: gene structure and biological activities. Cold Spring Harb Symp Quant Biol. 1986;51(Pt 1):597–609. doi: 10.1101/sqb.1986.051.01.072. [DOI] [PubMed] [Google Scholar]
  13. Havell E. A., Vilcek J. Production of high-titered interferon in cultures of human diploid cells. Antimicrob Agents Chemother. 1972 Dec;2(6):476–484. doi: 10.1128/aac.2.6.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Havell E. A., Yip Y. K., Vilcek J. Characteristics of human lymphoblastoid (Namalva) interferon. J Gen Virol. 1978 Jan;38(1):51–59. doi: 10.1099/0022-1317-38-1-51. [DOI] [PubMed] [Google Scholar]
  15. Hiscott J., Cantell K., Weissmann C. Differential expression of human interferon genes. Nucleic Acids Res. 1984 May 11;12(9):3727–3746. doi: 10.1093/nar/12.9.3727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kohase M., Henriksen-DeStefano D., May L. T., Vilcek J., Sehgal P. B. Induction of beta 2-interferon by tumor necrosis factor: a homeostatic mechanism in the control of cell proliferation. Cell. 1986 Jun 6;45(5):659–666. doi: 10.1016/0092-8674(86)90780-4. [DOI] [PubMed] [Google Scholar]
  17. Krieg P. A., Melton D. A. In vitro RNA synthesis with SP6 RNA polymerase. Methods Enzymol. 1987;155:397–415. doi: 10.1016/0076-6879(87)55027-3. [DOI] [PubMed] [Google Scholar]
  18. Marcus P. I., Sekellick M. J. Defective interfering particles with covalently linked [+/-]RNA induce interferon. Nature. 1977 Apr 28;266(5605):815–819. doi: 10.1038/266815a0. [DOI] [PubMed] [Google Scholar]
  19. Marcus P. I., Sekellick M. J. Interferon induction by viruses. XVI. 2-Aminopurine blocks selectively and reversibly an early stage in interferon induction. J Gen Virol. 1988 Jul;69(Pt 7):1637–1645. doi: 10.1099/0022-1317-69-7-1637. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Michie H. R., Manogue K. R., Spriggs D. R., Revhaug A., O'Dwyer S., Dinarello C. A., Cerami A., Wolff S. M., Wilmore D. W. Detection of circulating tumor necrosis factor after endotoxin administration. N Engl J Med. 1988 Jun 9;318(23):1481–1486. doi: 10.1056/NEJM198806093182301. [DOI] [PubMed] [Google Scholar]
  22. Munker R., Gasson J., Ogawa M., Koeffler H. P. Recombinant human TNF induces production of granulocyte-monocyte colony-stimulating factor. Nature. 1986 Sep 4;323(6083):79–82. doi: 10.1038/323079a0. [DOI] [PubMed] [Google Scholar]
  23. Nishizuka Y. The molecular heterogeneity of protein kinase C and its implications for cellular regulation. Nature. 1988 Aug 25;334(6184):661–665. doi: 10.1038/334661a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Patton J. S., Shepard H. M., Wilking H., Lewis G., Aggarwal B. B., Eessalu T. E., Gavin L. A., Grunfeld C. Interferons and tumor necrosis factors have similar catabolic effects on 3T3 L1 cells. Proc Natl Acad Sci U S A. 1986 Nov;83(21):8313–8317. doi: 10.1073/pnas.83.21.8313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Poupart P., Vandenabeele P., Cayphas S., Van Snick J., Haegeman G., Kruys V., Fiers W., Content J. B cell growth modulating and differentiating activity of recombinant human 26-kd protein (BSF-2, HuIFN-beta 2, HPGF). EMBO J. 1987 May;6(5):1219–1224. doi: 10.1002/j.1460-2075.1987.tb02357.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. 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]
  28. Schleef R. R., Bevilacqua M. P., Sawdey M., Gimbrone M. A., Jr, Loskutoff D. J. Cytokine activation of vascular endothelium. Effects on tissue-type plasminogen activator and type 1 plasminogen activator inhibitor. J Biol Chem. 1988 Apr 25;263(12):5797–5803. [PubMed] [Google Scholar]
  29. Seelentag W. K., Mermod J. J., Montesano R., Vassalli P. Additive effects of interleukin 1 and tumour necrosis factor-alpha on the accumulation of the three granulocyte and macrophage colony-stimulating factor mRNAs in human endothelial cells. EMBO J. 1987 Aug;6(8):2261–2265. doi: 10.1002/j.1460-2075.1987.tb02499.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Sung S. S., Jung L. K., Walters J. A., Chen W., Wang C. Y., Fu S. M. Production of tumor necrosis factor/cachectin by human B cell lines and tonsillar B cells. J Exp Med. 1988 Nov 1;168(5):1539–1551. doi: 10.1084/jem.168.5.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. 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]
  32. Wightman P. D., Raetz C. R. The activation of protein kinase C by biologically active lipid moieties of lipopolysaccharide. J Biol Chem. 1984 Aug 25;259(16):10048–10052. [PubMed] [Google Scholar]
  33. Williamson B. D., Carswell E. A., Rubin B. Y., Prendergast J. S., Old L. J. Human tumor necrosis factor produced by human B-cell lines: synergistic cytotoxic interaction with human interferon. Proc Natl Acad Sci U S A. 1983 Sep;80(17):5397–5401. doi: 10.1073/pnas.80.17.5397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Wong G. H., Goeddel D. V. Tumour necrosis factors alpha and beta inhibit virus replication and synergize with interferons. 1986 Oct 30-Nov 5Nature. 323(6091):819–822. doi: 10.1038/323819a0. [DOI] [PubMed] [Google Scholar]
  35. Ziegler E. J. Tumor necrosis factor in humans. N Engl J Med. 1988 Jun 9;318(23):1533–1535. doi: 10.1056/NEJM198806093182309. [DOI] [PubMed] [Google Scholar]
  36. Zinn K., DiMaio D., Maniatis T. Identification of two distinct regulatory regions adjacent to the human beta-interferon gene. Cell. 1983 Oct;34(3):865–879. doi: 10.1016/0092-8674(83)90544-5. [DOI] [PubMed] [Google Scholar]
  37. Zinn K., Keller A., Whittemore L. A., Maniatis T. 2-Aminopurine selectively inhibits the induction of beta-interferon, c-fos, and c-myc gene expression. Science. 1988 Apr 8;240(4849):210–213. doi: 10.1126/science.3281258. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES