γ-Interferon transcriptionally regulates an early-response gene containing homology to platelet proteins

Abstract

Interferons are a family of proteins first identified by their ability to induce cellular resistance to infection by many viruses. In addition to the antiviral properties it shares with the α- and β-interferons, γ-interferon (IFN-γ), a lymphokine secreted by activated T cells, activates macrophages, stimulates B cells, increases fibroblast and endothelial cell resistance to many non-viral intracellular parasites and modulates cell-surface proteins central to immune cell regulation1–13. To identify molecules involved in the IFN-γ response and characterize their modulation, we have isolated genes that are induced following recombinant IFN-γ treatment of U937 cells, a histiocytic lymphoma cell line with monocytic characteristics14,15. We report here the molecular cloning and characterization of a gene regulated by rIFN-γ in U937 cells as well as in human mononuclear cells, fibroblasts and endothelial cells. Messenger RNA from this gene is induced within 30 min of rIFN-γ treatment and demonstrates maximal (>30-fold) accumulation within 5 h. Increased transcription is partly responsible for this accumulation. This gene encodes a protein of relative molecular mass (Mr) 12,378 which has significant amino-acid homology to platelet factor-4 and β-thromboglobulin, two chemo-tatic proteins released by platelets on degranulation. This IFN-γ-inducible protein may be a member of a family of proteins involved in the inflammatory process.

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References

  1. 1

    Basham, T. Y. & Merigan, T. C. J. Immun. 130, 1492–1494 (1983).

    CAS  Google Scholar 

  2. 2

    Collins, T. et al. Proc. natn. Acad. Sci. U.S.A. 81, 4917–4921 (1984).

    ADS  CAS  Article  Google Scholar 

  3. 3

    Wallach, D., Fellous, M. & Revel, M. Nature 299, 833–836 (1982).

    ADS  CAS  Article  Google Scholar 

  4. 4

    Le, J. et al. J. Immun. 131, 2821–2826 (1983).

    CAS  PubMed  Google Scholar 

  5. 5

    Pace, J. L., Russell, S. W., Torres, B. A., Johnson, H. M. & Gray, P. W. J. Immun. 130, 2011–2013 (1983).

    CAS  Google Scholar 

  6. 6

    Schultz, R. M. & Kleinschmidt, W. J. Nature 305, 239–240 (1983).

    ADS  CAS  Article  Google Scholar 

  7. 7

    Nathan, C. F., Murray, H. W., Wiebe, M. E. & Rubin, B. Y. J. exp. Med. 155, 670–689 (1983).

    Article  Google Scholar 

  8. 8

    Murray, H. W., Rubin, B. Y. & Rothermel, C. D. J. clin. Invest. 72, 1506–1510 (1983).

    CAS  Article  Google Scholar 

  9. 9

    Leibson, J. H., Gefter, M., Zlotnik, A., Marrack, P. & Kappler, J. W. Nature 309, 799–801 (1984).

    ADS  CAS  Article  Google Scholar 

  10. 10

    Sidman, C. L., Marshall, J. D., Shultz, L. D., Gray, P. W. & Johnson, H. M. Nature 309, 799–801 (1984).

    ADS  Article  Google Scholar 

  11. 11

    Nakamura, M., Marser, T., Pewson, G. D. N., Daley, M. J. & Gette, M. L. Nature 307, 381–382 (1984).

    ADS  CAS  Article  Google Scholar 

  12. 12

    Pfefferkorn, E. R. Proc. natn. Acad. Sci. U.S.A. 81, 908–912 (1984).

    ADS  CAS  Article  Google Scholar 

  13. 13

    Turco, J. & Winkler, H. H. J. exp. Med. 158, 2159–2164 (1983).

    CAS  Article  Google Scholar 

  14. 14

    Sundstrom, C. & Nilsson, K. Int. J. Cancer 17, 565–577 (1976).

    CAS  Article  Google Scholar 

  15. 15

    Koren, H. S., Anderson, S. J. & Larrick, J. W. Nature 279, 328–331 (1979).

    ADS  CAS  Article  Google Scholar 

  16. 16

    Villa-Komaroff, L. et al. Proc. natn. Acad. Sci. U.S.A. 75, 3727–3731 (1978).

    ADS  CAS  Article  Google Scholar 

  17. 17

    Okayama, H. & Berg, P. Molec. cell. Biol. 2, 161–170 (1982).

    CAS  Article  Google Scholar 

  18. 18

    Celada, A., Gray, P. W., Rinderknecht, E. & Schreiber, R. D. J. exp. Med. 160, 55–74 (1984).

    CAS  Article  Google Scholar 

  19. 19

    Ringold, G. M. Biochim. biophys. Acta 560, 487–508 (1979).

    CAS  Google Scholar 

  20. 20

    Friedman, R. L., Manly, S. P., McMahon, M., Kerr, I. M. & Stark, G. R. Cell 38, 745–755 (1984).

    CAS  Article  Google Scholar 

  21. 21

    Larner, A. C. et al. Proc. natn. Acad. Sci. U.S.A. 81, 6733–6737 (1984).

    ADS  CAS  Article  Google Scholar 

  22. 22

    Sanger, F. & Coulson, A. R. J. J. molec. Biol. 94, 441–448 (1977).

    Article  Google Scholar 

  23. 23

    Maxam, A. M. & Gilbert, W. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).

    ADS  CAS  Article  Google Scholar 

  24. 24

    Perlman, D. & Halvorson, H. O. J. molec. Biol. 167, 391–409 (1983).

    CAS  Article  Google Scholar 

  25. 25

    Von Heijne, G. Eur. J. Biochem. 133, 17–21 (1983).

    CAS  Article  Google Scholar 

  26. 26

    Lipman, D. J. & Pearson, W. R. Science 227, 1435–1441 (1985).

    ADS  CAS  Article  Google Scholar 

  27. 27

    Begg, G. S., Pepper, D. S., Chesteman, C. N. & Morgan, F. J. Biochemistry 17, 1739–1744 (1978).

    CAS  Article  Google Scholar 

  28. 28

    Kaplan, K. L., Broekman, J. M., Chernoff, A., Lesznick, G. R. & Drillings, M. Blood 53, 604–618 (1979).

    CAS  PubMed  Google Scholar 

  29. 29

    Deuel, T. F. et al. Proc. natn. Acad. Sci. U.S.A. 78, 4584–4587 (1981).

    ADS  CAS  Article  Google Scholar 

  30. 30

    Senior, R. M., Griffin, G. L., Huang, J. S., Walz, D. A. & Deuel, T. F. J. cell. Biol. 96, 382–385 (1983).

    CAS  Article  Google Scholar 

  31. 31

    Hiti-Harper, J., Wohl, H. & Harper, E. Science 199, 991–992 (1978).

    ADS  CAS  Article  Google Scholar 

  32. 32

    Lonky, S. A. & Wohl, H. J. clin. Invest. 67, 817–826 (1981).

    CAS  Article  Google Scholar 

  33. 33

    Brindley, L. L., Sweet, J. M. & Goetzl, E. J. J. clin. Invest. 72, 1218–1223 (1983).

    CAS  Article  Google Scholar 

  34. 34

    Handin, R. I. & Cohen, H. J. J. biol. Chem. 251, 4273–4282 (1976).

    CAS  PubMed  Google Scholar 

  35. 35

    Hope, W., Martin, T. J., Chesteman, C. N. & Morgan, F. J. Nature 282, 210–212 (1979).

    ADS  CAS  Article  Google Scholar 

  36. 36

    Castor, W., Miller, J. W. & Walz, D. A. Proc. natn. Acad. Sci. U.S.A. 80, 765–769 (1983).

    ADS  CAS  Article  Google Scholar 

  37. 37

    Holt, J. C. & Niewiarowski, S. Biochim. biophys. Acta 632, 284–289 (1980).

    CAS  Article  Google Scholar 

  38. 38

    Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).

    CAS  Article  Google Scholar 

  39. 39

    Alwine, J. C., Kemp, D. J. & Stark, G. R. Proc. natn. Acad. Sci. U.S.A. 74, 5350–5354 (1977).

    ADS  CAS  Article  Google Scholar 

  40. 40

    Hofer, E. & Darnell, J. Cell 23, 585–593 (1981).

    CAS  Article  Google Scholar 

  41. 41

    Abulata, R., Ben-Zeev, A. & Alini, Y. J. molec. Biol. 172, 467–487 (1984).

    Article  Google Scholar 

  42. 42

    Kofatos, F. C., Jones, C. N. & Efstradiatis, A. Nucleic Acids Res. 7, 1541–1551 (1979).

    Article  Google Scholar 

  43. 43

    Sood, A. K., Pereira, D. & Weissman, S. M. Proc. natn. Acad. Sci. U.S.A. 78, 616–620 (1981).

    ADS  CAS  Article  Google Scholar 

  44. 44

    Lee, J. S. et al. Nature 299, 750–752 (1982).

    ADS  CAS  Article  Google Scholar 

  45. 45

    Dorner, M. H. et al. Proc. natn. Acad. Sci. U.S.A. (submitted).

  46. 46

    Parnes, J. R. et al. Proc. natn. Acad. Sci. U.S.A. 78, 2253–2257 (1981).

    ADS  CAS  Article  Google Scholar 

  47. 47

    Needleman, S. B. & Wunsch, C. D. J. molec. Biol. 48, 443–453 (1970).

    CAS  Article  Google Scholar 

  48. 48

    Kyte, J. & Doolittle, R. F. J. molec. Biol. 157, 105–132 (1982).

    CAS  Article  Google Scholar 

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Luster, A., Unkeless, J. & Ravetch, J. γ-Interferon transcriptionally regulates an early-response gene containing homology to platelet proteins. Nature 315, 672–676 (1985). https://doi.org/10.1038/315672a0

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