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. 1989 May;83(5):1570–1579. doi: 10.1172/JCI114054

Tumor necrosis factor and immune interferon synergistically induce cytochrome b-245 heavy-chain gene expression and nicotinamide-adenine dinucleotide phosphate hydrogenase oxidase in human leukemic myeloid cells.

M A Cassatella 1, L Hartman 1, B Perussia 1, G Trinchieri 1
PMCID: PMC303863  PMID: 2496143

Abstract

Recombinant tumor necrosis factor (rTNF) and rIFN-gamma induce in the human leukemia cell lines HL-60, ML3, and U937 the accumulation of transcripts of the X chromosome-linked chronic granulomatous disease (X-CGD) gene, encoding the 91-kD heavy chain of cytochrome b-245, a component of the NADPH oxidase of phagocytic cells. The gene is induced within 6 h by either cytokine, and its accumulation is observed upon induction with rIFN-gamma up to 5 d. The combined effect of the two cytokines is more than additive. rIFN-gamma also induces accumulation of X-CGD mRNA in immature myeloid cells from peripheral blood of chronic myeloid leukemia (CML) patients, whereas rTNF has almost no effect. The cells from CML patients constitutively express TNF mRNA, suggesting that endogenously produced TNF may play a role in the effect of rIFN-gamma on these cells. rTNF induces X-CGD gene expression in the myeloid cell lines acting, at least in part, at the transcriptional level, as shown in nuclear run-on experiments. The gene encoding the 22-kD light chain of cytochrome b-245 is constitutively expressed in the human myeloid cell lines and the accumulation of its transcripts is affected by neither rTNF nor rIFN-gamma, rTNF and rIFN-gamma synergistically to induce the cell lines to express the cytochrome b-245 heterodimer (as evaluated by its visible spectrum), and to produce NADPH oxidase activity and H2O2 upon stimulation with phorbol diesters.

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Selected References

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

  1. Andrew P. W., Robertson A. K., Lowrie D. B., Cross A. R., Jones O. T. Induction of synthesis of components of the hydrogen peroxide-generating oxidase during activation of the human monocytic cell line U937 by interferon-gamma. Biochem J. 1987 Nov 15;248(1):281–283. doi: 10.1042/bj2480281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Anegón I., Cuturi M. C., Trinchieri G., Perussia B. Interaction of Fc receptor (CD16) ligands induces transcription of interleukin 2 receptor (CD25) and lymphokine genes and expression of their products in human natural killer cells. J Exp Med. 1988 Feb 1;167(2):452–472. doi: 10.1084/jem.167.2.452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Babior B. M. The respiratory burst oxidase. Hematol Oncol Clin North Am. 1988 Jun;2(2):201–212. [PubMed] [Google Scholar]
  4. Baehner R. L., Kunkel L. M., Monaco A. P., Haines J. L., Conneally P. M., Palmer C., Heerema N., Orkin S. H. DNA linkage analysis of X chromosome-linked chronic granulomatous disease. Proc Natl Acad Sci U S A. 1986 May;83(10):3398–3401. doi: 10.1073/pnas.83.10.3398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Balsinde J., Mollinedo F. Specific activation by concanavalin A of the superoxide anion generation capacity during U937 differentiation. Biochem Biophys Res Commun. 1988 Mar 15;151(2):802–808. doi: 10.1016/s0006-291x(88)80352-8. [DOI] [PubMed] [Google Scholar]
  6. Barker K. A., Orkin S. H., Newburger P. E. Expression of the X-CGD gene during induced differentiation of myeloid leukemia cell line HL-60. Mol Cell Biol. 1988 Jul;8(7):2804–2810. doi: 10.1128/mcb.8.7.2804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Bellavite P., Dri P., Della Bianca V., Serra M. C. The measurement of superoxide anion production by granulocytes In whole blood. A clinical test for the evaluation of phagocyte function and serum opsonic capacity. Eur J Clin Invest. 1983 Aug;13(4):363–368. doi: 10.1111/j.1365-2362.1983.tb00114.x. [DOI] [PubMed] [Google Scholar]
  8. Berton G., Cassatella M. A., Bellavite P., Rossi F. Molecular basis of macrophage activation. Expression of the low potential cytochrome b and its reduction upon cell stimulation in activated macrophages. J Immunol. 1986 Feb 15;136(4):1393–1399. [PubMed] [Google Scholar]
  9. Berton G., Papini E., Cassatella M. A., Bellavite P., Rossi F. Partial purification of the superoxide-generating system of macrophages. Possible association of the NADPH oxidase activity with a low-potential (-247 mV) cytochrome b. Biochim Biophys Acta. 1985 Nov 27;810(2):164–173. doi: 10.1016/0005-2728(85)90132-x. [DOI] [PubMed] [Google Scholar]
  10. Berton G., Zeni L., Cassatella M. A., Rossi F. Gamma interferon is able to enhance the oxidative metabolism of human neutrophils. Biochem Biophys Res Commun. 1986 Aug 14;138(3):1276–1282. doi: 10.1016/s0006-291x(86)80421-1. [DOI] [PubMed] [Google Scholar]
  11. Cassatella M. A., Cappelli R., Della Bianca V., Grzeskowiak M., Dusi S., Berton G. Interferon-gamma activates human neutrophil oxygen metabolism and exocytosis. Immunology. 1988 Mar;63(3):499–506. [PMC free article] [PubMed] [Google Scholar]
  12. Cassatella M. A., Della Bianca V., Berton G., Rossi F. Activation by gamma interferon of human macrophage capability to produce toxic oxygen molecules is accompanied by decreased Km of the superoxide-generating NADPH oxidase. Biochem Biophys Res Commun. 1985 Nov 15;132(3):908–914. doi: 10.1016/0006-291x(85)91893-5. [DOI] [PubMed] [Google Scholar]
  13. Cassatella M. A., Valletta E., Dusi S., Berton G. Measurement of NADPH oxidase activity in detergent lysates of human and mouse macrophage monolayers. J Immunol Methods. 1986 Sep 27;92(2):231–240. doi: 10.1016/0022-1759(86)90171-7. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. Dayton E. T., Matsumoto-Kobayashi M., Perussia B., Trinchieri G. Role of immune interferon in the monocytic differentiation of human promyelocytic cell lines induced by leukocyte conditioned medium. Blood. 1985 Sep;66(3):583–594. [PubMed] [Google Scholar]
  16. Dayton E. T., Perussia B., Trinchieri G. Correlation between differentiation, expression of monocyte-specific antigens, and cytotoxic functions in human promyelocytic cell lines treated with leukocyte-conditioned medium. J Immunol. 1983 Mar;130(3):1120–1128. [PubMed] [Google Scholar]
  17. Defilippi P., Poupart P., Tavernier J., Fiers W., Content J. Induction and regulation of mRNA encoding 26-kDa protein in human cell lines treated with recombinant human tumor necrosis factor. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4557–4561. doi: 10.1073/pnas.84.13.4557. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Elias L., Wogenrich F. J., Wallace J. M., Longmire J. Altered pattern of differentiation and proliferation of HL-60 promyelocytic leukemia cells in the presence of leucocyte conditioned medium. Leuk Res. 1980;4(3):301–307. doi: 10.1016/0145-2126(80)90037-5. [DOI] [PubMed] [Google Scholar]
  19. Ezekowitz R. A., Dinauer M. C., Jaffe H. S., Orkin S. H., Newburger P. E. Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med. 1988 Jul 21;319(3):146–151. doi: 10.1056/NEJM198807213190305. [DOI] [PubMed] [Google Scholar]
  20. Ezekowitz R. A., Orkin S. H., Newburger P. E. Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous disease gene expression in X-linked variant chronic granulomatous disease. J Clin Invest. 1987 Oct;80(4):1009–1016. doi: 10.1172/JCI113153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gallagher R., Collins S., Trujillo J., McCredie K., Ahearn M., Tsai S., Metzgar R., Aulakh G., Ting R., Ruscetti F. Characterization of the continuous, differentiating myeloid cell line (HL-60) from a patient with acute promyelocytic leukemia. Blood. 1979 Sep;54(3):713–733. [PubMed] [Google Scholar]
  22. Krönke M., Schlüter C., Pfizenmaier K. Tumor necrosis factor inhibits MYC expression in HL-60 cells at the level of mRNA transcription. Proc Natl Acad Sci U S A. 1987 Jan;84(2):469–473. doi: 10.1073/pnas.84.2.469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lin J. X., Vilcek J. Tumor necrosis factor and interleukin-1 cause a rapid and transient stimulation of c-fos and c-myc mRNA levels in human fibroblasts. J Biol Chem. 1987 Sep 5;262(25):11908–11911. [PubMed] [Google Scholar]
  24. Michelson A. M., Markham A. F., Orkin S. H. Isolation and DNA sequence of a full-length cDNA clone for human X chromosome-encoded phosphoglycerate kinase. Proc Natl Acad Sci U S A. 1983 Jan;80(2):472–476. doi: 10.1073/pnas.80.2.472. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Newburger P. E., Speier C., Borregaard N., Walsh C. E., Whitin J. C., Simons E. R. Development of the superoxide-generating system during differentiation of the HL-60 human promyelocytic leukemia cell line. J Biol Chem. 1984 Mar 25;259(6):3771–3776. [PubMed] [Google Scholar]
  28. Ohno Y., Seligmann B. E., Gallin J. I. Cytochrome b translocation to human neutrophil plasma membranes and superoxide release. Differential effects of N-formylmethionylleucylphenylalanine, phorbol myristate acetate, and A23187. J Biol Chem. 1985 Feb 25;260(4):2409–2414. [PubMed] [Google Scholar]
  29. Palumbo A., Minowada J., Erikson J., Croce C. M., Rovera G. Lineage infidelity of a human myelogenous leukemia cell line. Blood. 1984 Nov;64(5):1059–1063. [PubMed] [Google Scholar]
  30. Parkinson J. F., Akard L. P., Schell M. J., Gabig T. G. Cell-free activation of phagocyte NADPH-oxidase: tissue and differentiation-specific expression of cytosolic cofactor activity. Biochem Biophys Res Commun. 1987 Jun 30;145(3):1198–1204. doi: 10.1016/0006-291x(87)91564-6. [DOI] [PubMed] [Google Scholar]
  31. Parkos C. A., Allen R. A., Cochrane C. G., Jesaitis A. J. The quaternary structure of the plasma membrane b-type cytochrome of human granulocytes. Biochim Biophys Acta. 1988 Jan 20;932(1):71–83. doi: 10.1016/0005-2728(88)90140-5. [DOI] [PubMed] [Google Scholar]
  32. Parkos C. A., Cochrane C. G., Schmitt M., Jesaitis A. J. Regulation of the oxidative response of human granulocytes to chemoattractants. No evidence for stimulated traffic of redox enzymes between endo and plasma membranes. J Biol Chem. 1985 Jun 10;260(11):6541–6547. [PubMed] [Google Scholar]
  33. Parkos C. A., Dinauer M. C., Walker L. E., Allen R. A., Jesaitis A. J., Orkin S. H. Primary structure and unique expression of the 22-kilodalton light chain of human neutrophil cytochrome b. Proc Natl Acad Sci U S A. 1988 May;85(10):3319–3323. doi: 10.1073/pnas.85.10.3319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Perussia B., Dayton E. T., Fanning V., Thiagarajan P., Hoxie J., Trinchieri G. Immune interferon and leukocyte-conditioned medium induce normal and leukemic myeloid cells to differentiate along the monocytic pathway. J Exp Med. 1983 Dec 1;158(6):2058–2080. doi: 10.1084/jem.158.6.2058. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Perussia B., Dayton E. T., Lazarus R., Fanning V., Trinchieri G. Immune interferon induces the receptor for monomeric IgG1 on human monocytic and myeloid cells. J Exp Med. 1983 Oct 1;158(4):1092–1113. doi: 10.1084/jem.158.4.1092. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Perussia B., Kobayashi M., Rossi M. E., Anegon I., Trinchieri G. Immune interferon enhances functional properties of human granulocytes: role of Fc receptors and effect of lymphotoxin, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor. J Immunol. 1987 Feb 1;138(3):765–774. [PubMed] [Google Scholar]
  37. Perussia B., Starr S., Abraham S., Fanning V., Trinchieri G. Human natural killer cells analyzed by B73.1, a monoclonal antibody blocking Fc receptor functions. I. Characterization of the lymphocyte subset reactive with B73.1. J Immunol. 1983 May;130(5):2133–2141. [PubMed] [Google Scholar]
  38. Pick E., Gadba R. Certain lymphoid cells contain the membrane-associated component of the phagocyte-specific NADPH oxidase. J Immunol. 1988 Mar 1;140(5):1611–1617. [PubMed] [Google Scholar]
  39. Roberts P. J., Cross A. R., Jones O. T., Segal A. W. Development of cytochrome b and an active oxidase system in association with maturation of a human promyelocytic (HL-60) cell line. J Cell Biol. 1982 Dec;95(3):720–726. doi: 10.1083/jcb.95.3.720. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Rossi F. The O2- -forming NADPH oxidase of the phagocytes: nature, mechanisms of activation and function. Biochim Biophys Acta. 1986 Nov 4;853(1):65–89. doi: 10.1016/0304-4173(86)90005-4. [DOI] [PubMed] [Google Scholar]
  41. Royer-Pokora B., Kunkel L. M., Monaco A. P., Goff S. C., Newburger P. E., Baehner R. L., Cole F. S., Curnutte J. T., Orkin S. H. Cloning the gene for an inherited human disorder--chronic granulomatous disease--on the basis of its chromosomal location. Nature. 1986 Jul 3;322(6074):32–38. doi: 10.1038/322032a0. [DOI] [PubMed] [Google Scholar]
  42. Schleicher E., Wieland O. H. Evaluation of the Bradford method for protein determination in body fluids. J Clin Chem Clin Biochem. 1978 Sep;16(9):533–534. [PubMed] [Google Scholar]
  43. Segal A. W. Absence of both cytochrome b-245 subunits from neutrophils in X-linked chronic granulomatous disease. Nature. 1987 Mar 5;326(6108):88–91. doi: 10.1038/326088a0. [DOI] [PubMed] [Google Scholar]
  44. Segal A. W., Garcia R., Goldstone H., Cross A. R., Jones O. T. Cytochrome b-245 of neutrophils is also present in human monocytes, macrophages and eosinophils. Biochem J. 1981 Apr 15;196(1):363–367. doi: 10.1042/bj1960363. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sottocasa G. L., Kuylenstierna B., Ernster L., Bergstrand A. An electron-transport system associated with the outer membrane of liver mitochondria. A biochemical and morphological study. J Cell Biol. 1967 Feb;32(2):415–438. doi: 10.1083/jcb.32.2.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Steeg P. S., Moore R. N., Johnson H. M., Oppenheim J. J. Regulation of murine macrophage Ia antigen expression by a lymphokine with immune interferon activity. J Exp Med. 1982 Dec 1;156(6):1780–1793. doi: 10.1084/jem.156.6.1780. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. 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]
  48. Takeda K., Iwamoto S., Sugimoto H., Takuma T., Kawatani N., Noda M., Masaki A., Morise H., Arimura H., Konno K. Identity of differentiation inducing factor and tumour necrosis factor. 1986 Sep 25-Oct 1Nature. 323(6086):338–340. doi: 10.1038/323338a0. [DOI] [PubMed] [Google Scholar]
  49. Thayer W. S., Rubin E. Molecular alterations in the respiratory chain of rat liver after chronic ethanol consumption. J Biol Chem. 1981 Jun 25;256(12):6090–6097. [PubMed] [Google Scholar]
  50. Tobler A., Johnston D., Koeffler H. P. Recombinant human tumor necrosis factor alpha regulates c-myc expression in HL-60 cells at the level of transcription. Blood. 1987 Jul;70(1):200–205. [PubMed] [Google Scholar]
  51. Trinchieri G., Kobayashi M., Rosen M., Loudon R., Murphy M., Perussia B. Tumor necrosis factor and lymphotoxin induce differentiation of human myeloid cell lines in synergy with immune interferon. J Exp Med. 1986 Oct 1;164(4):1206–1225. doi: 10.1084/jem.164.4.1206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Walther Z., May L. T., Sehgal P. B. Transcriptional regulation of the interferon-beta 2/B cell differentiation factor BSF-2/hepatocyte-stimulating factor gene in human fibroblasts by other cytokines. J Immunol. 1988 Feb 1;140(3):974–977. [PubMed] [Google Scholar]
  53. Yarden A., Kimchi A. Tumor necrosis factor reduces c-myc expression and cooperates with interferon-gamma in HeLa cells. Science. 1986 Dec 12;234(4782):1419–1421. doi: 10.1126/science.3097823. [DOI] [PubMed] [Google Scholar]

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