Skip to main content
Molecular and Cellular Biology logoLink to Molecular and Cellular Biology
. 1989 May;9(5):1922–1928. doi: 10.1128/mcb.9.5.1922

Molecular cloning of a gene selectively induced by gamma interferon from human macrophage cell line U937.

X D Fan 1, G R Stark 1, B R Bloom 1
PMCID: PMC362983  PMID: 2501656

Abstract

A cDNA clone encoding a gamma interferon (IFN-gamma)-inducible mRNA in human cells of the macrophage lineage was isolated and characterized. The corresponding gene, gamma.1, was selectively induced by IFN-gamma, responding a hundredfold better to IFN-gamma than to IFN-alpha. The induction was rapid and transient, with maximal mRNA accumulation at about 3 h and decline to the basal level after 48 h. Transcriptional activation could be detected as early as 5 min after IFN-gamma stimulation and accounted entirely for the mRNA accumulation. The induction of gamma.1 by IFN-gamma was cell-type restricted, being seen only in macrophages and endothelial cells. In addition, phorbol ester-induced differentiation of promyelocytic HL-60 cells and promonocytic THP-1 cells rendered the gamma.1 gene inducible by IFN-gamma. The 1.0-kilobase gamma.1 cDNA sequence encoded a small predicted polypeptide of 38 amino acids and had a conserved sequence associated with rapidly turning over mRNAs. In vitro translation of the gamma.1 transcript yielded a 4,000-dalton polypeptide.

Full text

PDF
1927

Images in this article

Selected References

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

  1. Aguet M., Dembić Z., Merlin G. Molecular cloning and expression of the human interferon-gamma receptor. Cell. 1988 Oct 21;55(2):273–280. doi: 10.1016/0092-8674(88)90050-5. [DOI] [PubMed] [Google Scholar]
  2. Basham T. Y., Merigan T. C. Recombinant interferon-gamma increases HLA-DR synthesis and expression. J Immunol. 1983 Apr;130(4):1492–1494. [PubMed] [Google Scholar]
  3. Benech P., Merlin G., Revel M., Chebath J. 3' end structure of the human (2'-5') oligo A synthetase gene: prediction of two distinct proteins with cell type-specific expression. Nucleic Acids Res. 1985 Feb 25;13(4):1267–1281. doi: 10.1093/nar/13.4.1267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Branca A. A., Baglioni C. Evidence that types I and II interferons have different receptors. Nature. 1981 Dec 24;294(5843):768–770. doi: 10.1038/294768a0. [DOI] [PubMed] [Google Scholar]
  5. Caput D., Beutler B., Hartog K., Thayer R., Brown-Shimer S., Cerami A. Identification of a common nucleotide sequence in the 3'-untranslated region of mRNA molecules specifying inflammatory mediators. Proc Natl Acad Sci U S A. 1986 Mar;83(6):1670–1674. doi: 10.1073/pnas.83.6.1670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  7. Collins S. J., Gallo R. C., Gallagher R. E. Continuous growth and differentiation of human myeloid leukaemic cells in suspension culture. Nature. 1977 Nov 24;270(5635):347–349. doi: 10.1038/270347a0. [DOI] [PubMed] [Google Scholar]
  8. Fan X. D., Goldberg M., Bloom B. R. Interferon-gamma-induced transcriptional activation is mediated by protein kinase C. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5122–5125. doi: 10.1073/pnas.85.14.5122. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Friedman R. L., Manly S. P., McMahon M., Kerr I. M., Stark G. R. Transcriptional and posttranscriptional regulation of interferon-induced gene expression in human cells. Cell. 1984 Oct;38(3):745–755. doi: 10.1016/0092-8674(84)90270-8. [DOI] [PubMed] [Google Scholar]
  10. Friedman R. M., Vogel S. N. Interferons with special emphasis on the immune system. Adv Immunol. 1983;34:97–140. doi: 10.1016/s0065-2776(08)60378-8. [DOI] [PubMed] [Google Scholar]
  11. Guyre P. M., Morganelli P. M., Miller R. Recombinant immune interferon increases immunoglobulin G Fc receptors on cultured human mononuclear phagocytes. J Clin Invest. 1983 Jul;72(1):393–397. doi: 10.1172/JCI110980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kelly J. M., Porter A. C., Chernajovsky Y., Gilbert C. S., Stark G. R., Kerr I. M. Characterization of a human gene inducible by alpha- and beta-interferons and its expression in mouse cells. EMBO J. 1986 Jul;5(7):1601–1606. doi: 10.1002/j.1460-2075.1986.tb04402.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Larner A. C., Jonak G., Cheng Y. S., Korant B., Knight E., Darnell J. E., Jr Transcriptional induction of two genes in human cells by beta interferon. Proc Natl Acad Sci U S A. 1984 Nov;81(21):6733–6737. doi: 10.1073/pnas.81.21.6733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Le J., Prensky W., Yip Y. K., Chang Z., Hoffman T., Stevenson H. C., Balazs I., Sadlik J. R., Vilcek J. Activation of human monocyte cytotoxicity by natural and recombinant immune interferon. J Immunol. 1983 Dec;131(6):2821–2826. [PubMed] [Google Scholar]
  15. Levy J. A., Virolainen M., Defendi V. Human lymphoblastoid lines from lymph node and spleen. Cancer. 1968 Sep;22(3):517–524. doi: 10.1002/1097-0142(196809)22:3<517::aid-cncr2820220305>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
  16. Luster A. D., Unkeless J. C., Ravetch J. V. Gamma-interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature. 1985 Jun 20;315(6021):672–676. doi: 10.1038/315672a0. [DOI] [PubMed] [Google Scholar]
  17. Luster A. D., Weinshank R. L., Feinman R., Ravetch J. V. Molecular and biochemical characterization of a novel gamma-interferon-inducible protein. J Biol Chem. 1988 Aug 25;263(24):12036–12043. [PubMed] [Google Scholar]
  18. Minowada J., Onuma T., Moore G. E. Rosette-forming human lymphoid cell lines. I. Establishment and evidence for origin of thymus-derived lymphocytes. J Natl Cancer Inst. 1972 Sep;49(3):891–895. [PubMed] [Google Scholar]
  19. Murray H. W., Byrne G. I., Rothermel C. D., Cartelli D. M. Lymphokine enhances oxygen-independent activity against intracellular pathogens. J Exp Med. 1983 Jul 1;158(1):234–239. doi: 10.1084/jem.158.1.234. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Nathan C. F., Murray H. W., Wiebe M. E., Rubin B. Y. Identification of interferon-gamma as the lymphokine that activates human macrophage oxidative metabolism and antimicrobial activity. J Exp Med. 1983 Sep 1;158(3):670–689. doi: 10.1084/jem.158.3.670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nathan C. F., Prendergast T. J., Wiebe M. E., Stanley E. R., Platzer E., Remold H. G., Welte K., Rubin B. Y., Murray H. W. Activation of human macrophages. Comparison of other cytokines with interferon-gamma. J Exp Med. 1984 Aug 1;160(2):600–605. doi: 10.1084/jem.160.2.600. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Newburger P. E., Ezekowitz R. A., Whitney C., Wright J., Orkin S. H. Induction of phagocyte cytochrome b heavy chain gene expression by interferon gamma. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5215–5219. doi: 10.1073/pnas.85.14.5215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nishizuka Y. The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature. 1984 Apr 19;308(5961):693–698. doi: 10.1038/308693a0. [DOI] [PubMed] [Google Scholar]
  24. Rovera G., Santoli D., Damsky C. Human promyelocytic leukemia cells in culture differentiate into macrophage-like cells when treated with a phorbol diester. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2779–2783. doi: 10.1073/pnas.76.6.2779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
  26. Staeheli P., Horisberger M. A., Haller O. Mx-dependent resistance to influenza viruses is induced by mouse interferons alpha and beta but not gamma. Virology. 1984 Jan 30;132(2):456–461. doi: 10.1016/0042-6822(84)90050-3. [DOI] [PubMed] [Google Scholar]
  27. Strunk R. C., Cole F. S., Perlmutter D. H., Colten H. R. gamma-Interferon increases expression of class III complement genes C2 and factor B in human monocytes and in murine fibroblasts transfected with human C2 and factor B genes. J Biol Chem. 1985 Dec 5;260(28):15280–15285. [PubMed] [Google Scholar]
  28. Sundström C., Nilsson K. Establishment and characterization of a human histiocytic lymphoma cell line (U-937). Int J Cancer. 1976 May 15;17(5):565–577. doi: 10.1002/ijc.2910170504. [DOI] [PubMed] [Google Scholar]
  29. Taylor J. Inhibition of interferon action by actinomycin. Biochem Biophys Res Commun. 1964;14:447–451. doi: 10.1016/0006-291x(64)90084-1. [DOI] [PubMed] [Google Scholar]
  30. Tsuchiya S., Kobayashi Y., Goto Y., Okumura H., Nakae S., Konno T., Tada K. Induction of maturation in cultured human monocytic leukemia cells by a phorbol diester. Cancer Res. 1982 Apr;42(4):1530–1536. [PubMed] [Google Scholar]
  31. Tsuchiya S., Yamabe M., Yamaguchi Y., Kobayashi Y., Konno T., Tada K. Establishment and characterization of a human acute monocytic leukemia cell line (THP-1). Int J Cancer. 1980 Aug;26(2):171–176. doi: 10.1002/ijc.2910260208. [DOI] [PubMed] [Google Scholar]
  32. Wallach D., Fellous M., Revel M. Preferential effect of gamma interferon on the synthesis of HLA antigens and their mRNAs in human cells. Nature. 1982 Oct 28;299(5886):833–836. doi: 10.1038/299833a0. [DOI] [PubMed] [Google Scholar]
  33. Weil J., Epstein C. J., Epstein L. B., Sedmak J. J., Sabran J. L., Grossberg S. E. A unique set of polypeptides is induced by gamma interferon in addition to those induced in common with alpha and beta interferons. Nature. 1983 Feb 3;301(5899):437–439. doi: 10.1038/301437a0. [DOI] [PubMed] [Google Scholar]

Articles from Molecular and Cellular Biology are provided here courtesy of Taylor & Francis

RESOURCES